IMAGE  EVALUATION 
TEST  TARGET  (MT-3) 


Zi 


1.0 


I.I 


Ki  K    12.2 
£|S4    ■- 

1.8 


■ 

1.25    ||.4      1.6 

^ 

6"     

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Photographic 

Sciences 

Corporation 


A 


<^ 


23  WEST  MAIN  STREET 

WEBSTER,  N.Y.  14580 

(716)  872-4503 


0 


1 


CIHM/ICMH 

Microfiche 

Series. 


CiHM/ICMH 
Collection  de 
microfiches. 


Canadian  Institute  for  Historical  Microreproductions  /  institut  Canadian  de  microreproductions  historiques 


Technical  and  Bibliographic  Notes/Notes  techniques  et  bibliographiquas 


The  Institute  has  attempted  to  obtain  the  best 
original  copy  available  for  filming.  Features  of  this 
copy  which  may  be  bibliographically  unique, 
which  may  alter  any  of  the  images  in  the 
reproduction,  or  which  may  significantly  change 
the  usual  method  of  filming,  are  checked  below. 


0 


D 


D 


D 
D 


D 


D 


Coloured  covers/ 
Couverture  de  couleur 


I      I    Covers  damaged/ 


Couverture  endommag^e 


Covers  restored  and/or  laminated/ 
Couverture  restaurie  et/ou  pellicul6e 


r~1    Cover  title  missing/ 


Le  titre  de  couverture  manque 


I      I    Coloured  maps/ 


Cartes  giographiques  en  couleur 


Coloured  inic  (i.e.  other  than  blue  or  blacic)/ 
Encre  de  couleur  (i.e.  autre  que  bieue  ou  noire) 


I      I    Coloured  plates  and/or  illustrations/ 


Planches  et/ou  illustrations  en  couleur 

Bound  with  other  material/ 
Reli6  avec  d'autres  documents 

Tight  binding  may  cause  shadows  or  distortion 
along  interior  margin/ 

La  re  Mure  serrie  peut  causer  de  I'ombre  ou  de  la 
distortion  le  long  de  ia  marge  intdrieure 

Biani(  leaves  added  during  restoration  may 
appear  within  the  text.  Whenever  possible,  these 
have  been  omitted  from  filming/ 
II  se  peut  que  certaines  pages  blanches  ajouties 
lors  d'une  restauration  apparaissent  dans  le  texte, 
mais,  lorsque  cela  itait  possible,  ces  pages  n'ont 
pas  dtd  filmdes. 

Additional  comments:/ 
Commentaires  suppldmentaires; 


L'Institut  a  microfilm^  le  meilleur  exemplaire 
qu'il  lui  a  M  possible  de  se  procurer.  Les  details 
de  cet  exemplaire  qui  sont  peut-dtre  uniques  du 
point  de  vue  bibliographique,  qui  peuvent  modifier 
une  image  reproduite,  ou  qui  peuvent  exiger  une 
modification  dans  la  mithode  normale  de  filmage 
sont  indiquds  ci-dessous. 


I      I    Coloured  pages/ 


D 


Pages  de  couleur 

Pages  damaged/ 
Pages  endommagies 

Pages  restored  and/oi 

Pages  restaurdes  et/ou  pelliculdes 

Pages  discoloured,  stained  or  foxe< 
Pages  d6color6es,  tachetdes  ou  piqudes 

Pages  detached/ 
Pages  ddtachdes 

Showthrough/ 
Transparence 

Quality  of  prir 

Quality  in6gale  de  I'impression 

Includes  supplementary  materii 
Comprend  du  materiel  suppl^mentaire 

Only  edition  available/ 
Seule  Edition  disponible 


r~~\  Pages  damaged/ 

I      I  Pages  restored  and/or  laminated/ 

r^  Pages  discoloured,  stained  or  foxed/ 

I      I  Pages  detached/ 

ry]  Showthrough/ 

I      I  Quality  of  print  varies/ 

I      I  Includes  supplementary  material/ 

I     I  Only  edition  available/ 


1 

s 
7 

V 

d 

•I 
b 
ri 
r( 
nr 


Pages  wholly  or  partially  obscured  by  errata 
slips,  tissues,  etc.,  have  been  refilmed  to 
ensure  the  best  possible  image/ 
Les  pages  totaiement  ou  partiellement 
obscurcies  par  un  feuillet  d'errata,  une  pelure, 
etc.,  ont  M  filmdes  d  nouveau  de  fa^on  i 
obtenir  la  meilleure  image  possible. 


This  item  is  filmed  at  the  reduction  ratio  checked  below/ 

Ce  document  est  filmd  au  taux  de  reduction  indiqui  ci-dessous. 

10X  14X  18X  22X 


26X 


30X 


y 

12X 


16X 


20X 


24X 


28X 


32X 


Th«  copy  filmed  h«r«  has  b««n  raproduead  thanks 
to  tha  ganaroaity  of : 

Medical  Library 
McGill  University 
Montreal 

Tha  imagaa  appaaring  hara  Bf  tha  baat  quality 
poaaibia  considaring  tha  condition  and  lagibility 
of  tha  original  copy  and  In  kaaping  with  tha 
filming  contract  spaciflcationa. 


Original  copias  in  printad  papar  covara  ara  filmad 
beginning  with  tha  front  covar  and  ending  on 
tha  last  page  with  a  printad  or  llluatrated  imprea- 
aion,  or  tha  back  covar  whan  appropriate.  Ail 
other  original  copiaa  ara  filmad  beginning  on  the 
f  irat  page  with  a  printad  or  llluatrated  imprea- 
slon,  and  ending  on  the  laat  page  with  a  printad 
or  Illustrated  Impression. 


L'exemplaira  fllmi  fut  reprodult  grAce  k  la 
gAnirositi  da: 

Medical  Library 
McGill  University 
Montreal 

Lea  imagaa  suhrantea  ont  AtA  raproduitea  avac  la 
plus  grand  soin.  compta  tenu  de  la  condition  at 
da  la  nattet*  da  l'exemplaira  filmi,  at  en 
conformit*  avac  las  conditions  du  eontrat  da 
fiimage. 

Lea  exemplairea  orlginaux  dont  la  couverture  en 
papier  eat  Imprimte  sont  fllmis  en  commenpant 
par  la  premier  plat  at  an  terminant  soit  par  la 
darnlAre  page  qui  comporta  une  empreinte 
d'Impreaalon  ou  d'liluatration.  soit  par  la  second 
plat,  selon  le  eaa.  Toua  lea  autrea  exemplairea 
orlginaux  sont  filmto  an  commenpant  par  la 
premiere  page  qui  comporta  une  empreinte 
d'Impreaalon  ou  d'lliustratlon  at  an  terminant  par 
la  darnlAre  page  qui  comporta  une  telle 
empreinte. 


The  last  recorded  frame  on  each  microfiche 
shall  contain  the  symbol  — »>  (meaning  "CON- 
TINUED"), or  the  symbol  V  (meaning  "END"), 
whichever  appiiaa. 


Un  dee  symbolaa  suivanta  apparaftra  sur  la 
darnlAre  image  de  cheque  microfiche,  selon  le 
caa:  le  symbols  -*>  signlfle  "A  SUIVRE",  le 
symbols  ▼  signifie  "FIN". 


Mapa,  piataa.  charts,  etc.,  may  be  filmed  at 
different  reduction  ratios.  Thoaa  too  large  to  be 
entirely  Included  In  one  expoaure  ara  filmed 
beginning  In  the  upper  left  hand  corner,  left  to 
right  and  top  to  bottom,  aa  many  frames  as 
required.  The  following  diagrama  iiluatrate  the 
method: 


Lea  cartas,  planches,  tableaux,  etc.,  peuvent  Atre 
flimia  A  dee  taux  da  rMuctlon  diff^rants. 
Lorsque  le  document  eat  trop  grand  pour  Atra 
reprodult  en  un  seul  cllchA,  11  est  film*  A  partir 
de  I'angia  supArieur  gauche,  de  gauche  A  droite, 
et  de  haut  an  baa.  en  prenant  la  nombra 
d'Imagas  nAcessaira.  Lea  diagrammas  suivanta 
illustrant  la  mAthoda. 


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J.  afiORGE  AfaAMI,  iil.A.,  M.I>.  (Camb.), 

Professor  ot  Pathblogy,  McGill  University, 
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BEliSIG    THE  .  MIt>DLETON  .  GOLDSMITH    LEG- 

Litres  FOR  the  year  isge.  delivered' 

BE^ORte    THE    pathological    SOCIETY 
-     OF   NEW  M  REPRINTED  FROM 

THE    MEDICAJi   RECORD  OF   MARCH   14TH 
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ON  THE  RELATIONSHIP  BETWEEN 
INFLAMMATION  AND  SUNDRY 
FORMS   OF   FIBROSIS. 


BY 


J.  GEORGE    ADAMI,  M.A.,  M.D.  (Camb.), 

Professor  of  Pathology,  McGill  University, 
Montreal. 


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BEING  THE  MIDDLETON  -  GOLDSMITH  LEC- 
TURES FOR  THE  YEAR  1896,  DELIVERED 
BEFORE  THE  PATHOLOGICAL  SOCIETY 
OF  NEW  YORK,  AND  REPRINTED  FROM 
THE  MEDICAL  RECORD  OF  MARCH  14TH 
AND  21ST,  AND  APRIL  4TH  AND  iith. 


' 


.  ,. 


New  Youk:    The  Publishers'  Printing  Company,  isae. 


'":\:i^< 


MIDDLETON-GOLDSMITH  LECTURES  '—ON 
THE  RELATIONSHIP  BETWEEN  INFLAM- 
MATION AND  SUNDRY  FORMS  OF  FI- 
BROSIS. 


By  J.  GEORGE  ADAMI,  M.A.,  M.D.  Camh., 

PROFESSOR   OF    PATHOLOGY,    m'gII.I.    UNIVF.KSITV,    MONTREAL. 

Mr.  President  and  Gentlemen:  I  cannot  proceed 
to  the  delivery  of  these  lectures  without  in  the  first 
place  extolling  the  beneficence  of  him  throucjh  whose 
regard  for  this  society  and  generosity  it  has  been 
made  possible  for  you  to  institute  this  series  of  lec- 
tures— of  him  whom  thus  you  are  bound  to  keep  in  ever 
green  remembrance.  And  in  the  second  place  I  owe 
it  not  only  to  you  but  to  myself  to  give  utterance  to 
my  very  sincere  gratitude  for  the  honor  done  me  in 
inviting  me  to  attempt  to  fill  a  position  in  which  al- 
ready the  great  pathologists  of  this  continent  have  one 
after  the  other  added  new  leaves  to  their  laurels.  For 
myself  I  cannot  hope  to  vie  with  my  illustrious  pre- 
decessors. I  can  but  exceed  them  in  appreciati  n  of 
the  honor  done  to  me,  and  through  me  to  the  city  •  nd 
university  of  my  adoption.  I  feel  acutely  your  kind- 
ness in  thus  inviting  to  deliver  these  lectures  one 
who  is  a  stranger  among  you,  one  who  as  yet  can 
scarce  feel  himself  other  than  a  stranger  to  this  con- 
tinent. For  my  university  it  does  not  need  that  I  should 
be  specially  empowered  to  announce  to  you  how,  striv- 
ing toward  higher  things,  that  university  appreciates 
and  is  encouraged  by  every  act  of  recognition  from 
the  larger  world. 

It  might,  perhaps,  sir,  be  expected  by  that  larger 

'  Delivered  before  the  New  ^'ork   l\'itliological  Society. 


world  that  I  should  here  make  due  and  telling  refer- 
ence to  my  presence  among  you  at  the  present  epoch, 
I  am  inclined  to  think  that  when  the  universality  of 
science  and  our  common  brotherhood  in  it  are  so  ob- 
vious to  all  of  us,  and  the  insistence  thereupon  is  to  us 
so  much  of  a  truism,  it  were  almost  an  insult  to  your 
intelligence  and  good  will  did  1  say  anything,  how- 
ever much  I  may  personally  appreciate  your  kind  in- 
vitation at  this  especial  juncture.  The  most  I  dare 
venture  is  to  express  the  fervent  wish  that  the  same 
fellowship  may  bind  together  the  nations  which  now 
unites  all  those  striving  after  good  works  in  all  branches 
of  science. 

Throughout  the  days  of  this  generation,  and  to  an 
increasing  extent  in  these  latter  days,  there  has  been 
and  there  continues  to  be  a  lively  discussion  as  to 
what  is  and  what  is  not  to  be  included  in  the  scope  of 
inflammation.  And  as  of  late  among  a  narrow  sect  of 
surgeons  or  surgical  pathologists  there  has  been  mani- 
fest the  revival  of  what,  were  I  a  theologian,  I  should 
denominate  a  (not  unqualified)  heresy,  but  what,  as  a 
pathologist,  I  prefer  to  describe  as,  in  my  opinion,  a 
serious  misconception,  I  have  thought  it  well,  not  only 
from  the  interest  excited  by  the  subject  in  our  body 
but  also  from  the  recrudescence  of  this  misconception, 
to  select  as  the  subject  of  these  lectures  this  matter  of 
inflammation  and  the  relationship  existing  between  it 
and  fibrosis  or  fibrous  hyperplasia  in  its  various  forms. 

Even  at  the  best  this  is  a  subject  involved  in  diffi- 
culties. How  involved  I  did  not  wholly  realize  until 
some  months  ago  I  was  called  upon  by  my  friend. 
Prof.  Clifford  Allbutt,  of  Cambridge,  England,  to  dis- 
cuss the  matter  succinctly  in  the  course  of  an  article 
upon  the  "  Pathology  of  Inflammation  in  General," 
and  was  forced  to  face  the  matter  straightly.  As  I 
doubt  not,  most  here  present  have  found  it  is  one  thing 
to  have  general  opinions,   another  to  place  them  in 


i 

■i 


in 


logical  sequence  upon  paper.  When  I  came  to  at- 
tempt the  latter,  and  again  lo  consult  the  accounts 
given  in  the  leading  articles  and  text-books,  I  discov- 
ered not  only  the  inconsequential  nature  of  many  of 
my  previous  views  but  also  that  most  of  what  had  al- 
ready been  written  read  like  the  writing  of  scribes 
rather  than  of  those  having  authority;  and  after  having 
written  the  article  or  section  of  an  article  alreadv  re- 
ferred  to  I  cannot  but  feel  that  what  is  there  stated 
merits  the  same  reproach,  and  since  the  manuscript 
left  my  hands  the  more  I  have  deliberated  the  more 
dissatisfied  have  I  felt  over  my  own  writing.  I  am 
glad  to  have  this  opportunity  to  revise  and  advance 
my  views  upon  the  subject,  and  even  before  the  article 
in  question  is  published  to  amend  it  and  carry  to  a 
more  logical  conclusion  the  treatment  of  the  princi- 
ples upon  which  the  article  is  based.  I  cannot  hope 
to  solve  all  or  any  of  the  problems  that  a  study  of  this 
relationship  between  inflammation  and  fibrous-tissue 
growth  opens  up;  at  most,  suggesting  rather  than  dic- 
tating, I  may  possibly  help  others  toward  solution  and 
may  indicate  the  lines  along  which  future  research 
would  seem  to  promise  satisfactory  results. 

We  are  accustomed  to  employ  the  termination  "  itis" 
with  the  prefix  "chronic"  in  almost  if  not  quite  every 
case  in  which  there  is  replacement  of  the  cell  ele- 
ments proper  of  a  tissue  by  new  fibrous-tissue  growth. 
That  is  to  say,  we  assume  all  these  conditions  to  be  of 
like  origin,  to  be  manifestations  of  chronic  inflamma- 
tion, or  as  the  attempt  at  repair  following  upon  acute 
inflammation. 

Fibroid  areas  in  the  heart  muscle  are  all  grouped 
together  under  the  convenient  term  of  chronic  inter- 
stitial myocarditis.  Fibrosis  of  the  valves  of  the 
heart  with  its  sequelae  we  speak  of  as  chronic  endo- 
carditis. Arteriosclerosis  is  indifferently  spoken  of 
as  chronic  arteritis  or  endarteritis.  Whatever  the 
form  of  fibroid  change   occurring   in    the  kidney,   it 


comt's  under  the  hca(lin<j;  of  chronic  interstitial  ne- 
piiritis.  In  the  case  of  tlie  liver  it  is  true  the  conven- 
iently non-committal  name  of  cirrhosis  is  in  Knglish- 
speakinj;  countries  the  term  most  usually  employed  to 
denote  libroid  chan^je,  yet  there  are  not  wanting  those 
who  speak  of  chronic  interstitial  hepatitis. 

1  might  similarly  pass  in  order  organ  after  organ 
of  the  body,  with  its  chronic  "-itis."  Lax  indeed  is 
the  employment  of  this  common  denomination  of 
chronic  inflammation,  and  its  sole  merit  is  its  conven- 
ience in  cloaking  our  ignorance  of  the  exact  causa- 
tion of  most  of  the  conditions  to  which  it  is  applied. 
In  these  lectures  I  wish  to  discuss  how  far  and  in 
what  cases  we  are  justified  in  the  employment  of  the 
term,  and  to  what  extent  the  development  of  fibrous 
tissue  in  the  more  noble  organs  of  the  body  is  the  re- 
sult of  inrtammatory  disturbance. 

In  such  a  discussion  everything  depends  upon  the 
definition  of  inflammation  which  is  found  acceptable, 
and  the  conclusions  reached  must  stand  or  fall  in  the 
exact  ratio  in  which  the  definition  enunciated  com- 
mends itself  to  other  workers.  Thus,  first,  it  will  be 
absolutely  necessary  for  me  to  state  clearly  and  dis- 
tinctly what  I  understand  by  the  term  "  infiammation." 

Two  courses,  it  seems  to  me,  and  only  two  are  open 
to  us  with  regard  to  our  appreciation  of  the  term. 
Either  we  can,  with  Thoma,  agree  that  it  is  so  unsat- 
isfactory and  that  the  discussions  which  have  arisen 
as  to  its  scope,  or,  more  truly,  as  to  the  processes  that 
are  rightly  to  be  included  under  the  term,  are  so  bar- 
ren and  profitless  that  we  decide  absolutely  to  expunge 
it  from  our  vocabulary;  or,  on  the  other  hand,  we 
must  determine  to  include  in  our  idea  of  inflamma- 
tion all  processes  having  a  like  origin  and  tendency. 
There  is  no  logical  intermediate  course  unless  it  be 
to  confine  the  term  strictly  to  its  primitive  meaning 
and  to  determine  that  there  can  be  inflammation  only 
where  there  is  "flaming,"  where  there  is  redness  and 


heat.  No  one  is  prepared  nowadays  to  take  this 
course,  for  this  necessitates  physiol()p;ical  active  con- 
<j;estion  of  a  superficial  or^an  being  considered  as  in- 
Hamniatory.  Sfor  ajjain  are  there  many  who,  wedded 
to' tradition  and  cardinally  virtuous,  with  Celsus  only 
see  inHanimation  when  rubor,  calor,  dolor,  and  tumor 
are  present.  For  these  cannot  deny  that  identical 
processes  may  occur  when  one  or  two  or  more  of  these 
cardinal  symptoms  are  wanting.  Thus,  nowadays, 
those  who  would  define  inflammation  etymologically 
are  non-existent,  while  the  partisans  of  tradition  are 
"  minished  and  brought  low,"  forming  a  small  and  an 
impossible  remnant.  Hence,  to  return  to  my  previous 
statement,  there  are  but  two  logical  courses  open  to 
us.  Can  we  accept  the  first  alternative  and  banish 
the  idea  of  inflammation?  I  trow  not — the  suggestion 
is  too  quixotic.  It  is  not  within  the  power  of  any 
workers  in  any  one  branch  of  our  science,  even  if  that 
branch  be  pathology,  to  expunge  at  will  a  term  of  uni- 
versal employment,  a  term  that  has  come  down  to  us 
through  the  ages — a  term  which,  however  loosely  and 
variously  employed,  does  nevertheless  for  all  cover  a 
greater  or  less  number  of  processes  of  common  oc- 
currence. We  cannot  in  a  widespread  science  sud- 
denly create  a  "tabula  rasa"  and  start  anew.  Just  as 
were  we  to  do  away  with  the  plutocracy  and  start 
equally  endowed  with  worldly  possessions,  while  in 
twenty  years  the  old  plutocratic  families  would  per- 
chance be  non-existent  as  such,  yet  the  amassing  of 
money  and  possessions  in  the  hands  of  a  few  would 
inevitably  be  manifested,  so  were  we  to  banish  "in- 
flammation" from  our  vocabulary,  in  the  same  time  or 
even  less  some  other  word  would  be  surely  in  common 
employment  to  denote  the  same  idea.  It  cannot  be 
done,  and  as  a  consequence  the  adoption  of  the  second 
alternative  is  our  only  practical  course. 

We  have,  that  is  to  say,  so  to  employ  the  term  that 
it  will  embrace  all  processes  having  a  like  origin  and 


like  import.  Thus,  then,  starting  from  the  generally 
accepted  basis  that  the  process  is  in  its  essence  local 
and  that  the  prime  cause  of  all  inflammations  is  in- 
jury to  the  tissues,  if  we  are  prepared  to  admit  that  one 
common  or  allied  train  of  results  follows  upon  all  in- 
juries, we  must  as  our  provisional  definition  state  that 
inflammation  is  the  series  of  changes  constituting  the 
local  reaction  to  injury. 

This  is  to  all  intents  and  purposes  Burdon-Sander- 
son's  definition  and  is  that  which  for  the  last  quarter 
of  a  century  has  been  most  generally  accepted.  For 
myself  1  cordially  accept  it  as  a  good  working  defini- 
tion ;  but  at  the  same  time  I  cannot  but  consider  that 
the  researches  made  since  1880  have  materially  added 
to  our  comprehension  of  the  phenomena  associated 
with  the  process  and  of  their  tendency,  and  permit  us 
now  to  acknowledge  the  import  as  well  as  the  origin 
of  the  process.  Those  researches  have  shown  us  that 
a  very  definite  meaning  is  to  be  attached  to  the  main 
vital  processes  which  follow  injury  to  a  part.  They 
have  proved  that  the  accumulation  of  leucocytes  in  the 
injured  area  is  purposeful ;  that,  whether  by  intra-  or 
extra-cellular  action,  these  cells  are  capable,  up  to  a 
certain  extent,  of  counteracting  the  irritant  and  of  re- 
moving dead  and  effete  material ;  they  have  satisfac- 
torily proved  that  the  inflammatory  serum  possesses 
both  digestive  and  bactericidal  powers  greater  than 
the  serum  of  the  circulating  blood;   they  have  demon- 


strated that  the 


migration 


of  the  leucocvtes  into  the 


inflammatory  area  is  not  a  passive  process,  but  an  ac- 
tive one  directly  dependent  upon  the  extent  of  the 
stimulus  exerted  upon  these  cells  by  chemical  altera- 
tions in  their  environment;  thev  have  demonstrated 
that  the  amount  of  fluid  exuded  into  any  one  region 
of  the  body  varies  inter  alia  directly  according  to  the 
intensity  of  the  irritant — the  more  intense  the  irritant 
the  greater  the  extent  to  which  it  is  diluted;  while, 
further,  the  part  played  by  the  fixed  cells  in  the  im- 


mediate  neighborhood  is  equally  evident  and  equally 
purposeful,  tending  manifestly  to  result  in  the  cutting 
off  of  the  damaged  area  from  the  surrounding  healthy 
tissue  and  again  to  replace  the  tissue  that  has  under- 
gone destruction.  Hence  I  am  impelled  to  define  in- 
flammation as  the  local  attempt  at  repair  of  injury, 
or,  more  fully,  inasmuch  as  there  is  a  certain  small 
class  of  cases  in  which  all  the  symptoms  of  inflamma- 
tion are  present  as  a  consequence  of  nervous  disturb- 
ance wholly  unassociated  with  previous  local  injury,' 
as  the  scries  of  chcviges  uiJiich  constitute  the  local  at- 
tempt at  repair  of  actual  or  referred  injury  to  a  part. 
So  that  needless  objections  be  not  raised,  let  me  em- 
phasize the  fact  that  I  do  not  regard  inflammation  as 
synonymous  with  repair.  Attempt  at  repair  and  repair 
are  two  very  different  things,  and  no  more  to  be  con- 
founded than  attempted  suicide  and  suicide,  or,  not 
to  approach  too  closely  to  a  very  delicate  subject,  than 
the  Emperor  William's  recent  telegram  to  the  Boers 
and  actual  war  between  two  considerable  European 
nations. 

This,  then,  is  the  definition  I  am  inclined  to  lay 
down.  Save  in  the  small  matter  of  the  wording,  I  do 
not  claim  any  originality,  for  others  in  different  lands 
have  given  forth  definitions  embracing  the  same  idea. 
Thus  Neumann,  in  Germany,  defines  inflammation  as 
'"  the  series  of  local  phenomena  which  are  developed 
in  consequence  of  primary  lesions  of  the  tissues  and 
which  tend  to  heal  these  lesions."  '"  Bland  Srtton,  in 
England,  is  somewhat  more  restricted.  ''  It  is,"  says 
he,  "the  method  by  which  an  organism  attempts  to 

'  The  most  striking  example  of  this  class  is  to  be  seen  in  the 
experiment  which  has  been  frequently  repeated,  among  others  by 
my  colleague,  Dr.  James  Stewart,  of  assuring  a  susceptible  in- 
dividual under  hypnotic  influence  that  the  hand  or  other  region 
has  been  burned  or  blistered,  when  within  a  very  short  period 
the  part  becomes  reddened,  swollen,  and,  it  may  be,  the  seat  of 
marked  serous  effusion. 

■■'Ziegler's  "Beitriige,"  v.,  1889,  p.  347. 


8 


^\ 


J! 


render  inert  noxious  elements  introduced  from  without 
or  arising  within  it."  '  I  doubt  whether  Sutton  is 
right  in  speaking  of  it  as  a  method  and  to  me  the 
larger  view  appeals,  not  simply  of  counteraction 
against  the  irritant  but  also  of  attempt  to  bring  about 
a  return  of  the  region  toward  a  functional  condition — 
but  the  definition  contains  the  same  recognition  of  the 
purposive  nature  of  the  process.  And  lastly,  here  at 
home,  Councilman  acknowledges  the  same.  In  his 
most  lucid  article  in  Dennis'  "  System  of  Surgery"  he 
defines  inflammation  as  "  the  sum  of  the  phenomena 
which  take  place  in  the  tissue  as  the  effect  of  an  in- 
jury. The  object  of  these  various  phenomena  is  to 
overcome  or  to  diminish  the  effects  of  the  injury." " 

Whatever  justice  there  might  have  been  a  few  years 
ago  in  the  objection  that  this  view  of  inflammation  is 
teleological,  now,  with  the  facts  at  our  disposal,  the 
objection  is  no  longer  valid.  As  well  may  the  state- 
ment that  the  function  of  the  heart  is  to  propel  the 
blood  into  the  arteries  be  condemned  as  teleological, 
or  objection  be  taken  to  the  statement  that  digestion 
is  the  series  of  processes  whereby  matters  received 
into  the  alimentary  tract  tend  to  be  converted  to  the 
uses  of  the  tissues  of  the  body.  We  are  ready  enough 
to  admit  the  deductions  drawn  from  physiological  ex- 
periments; we  must  equally  accept  the  results  of  ex- 
perimental pathology. 

But  the  definition  here  enunciated  is  altogether  too 
broad  for  many  to  accept,  and  ever  since  Hiiter  pro- 
pounded the  view  that  the  term  inflammation  ought  to 
be  restricted  to  those  conditions  in  which  there  is  in- 
fection by  micro-organisms,  with  pus  formation,  there 
have  not  been  wanting  adherents  of  the  narrower  view. 
And  as  what  is  to  follow  must  largely  stand  or  fall  ac- 
cording to  the  acceptance  of  the  definition  herein  set 

'  I  here  quote  from  Professor  Senn,  not  having  been  able  to 
discover  the  original  passage. 

'■^Dennis'  "System,"  vol.  '.,  1895,  p.  144. 


1 


forth,  and  inasmuch  as  this  confounding  of  infection 
and  pyogenesis  with  inflammation  appears  to  be  grow- 
ing more  and  more  popular  upon  this  continent,  I 
needs  must  for  a  short  time  discuss  the  propriety  and 
soundness  of  the  movement. 

I  do  this,  sir,  with  some  hesitation,  for  I  feel  that 
I  am  reverting  to  very  elementary  pathology;  never- 
theless it  is  just  because  the  matter  is  so  elementary, 
so  fundamental,  so  all-important  for  a  right  compre- 
hension of  all  pathology,  and  because  the  distinction 
with  which  you  have  honored  me  affords  an  almost 
unique  opportunity  for  calling  attention  to  this  mat- 
ter, that  I  make  bold  to  utilize  this  opportunity  to 
urge  a  broad  and  logical  consideration  of  the  subject. 
Dr.  Senn,  professor  of  the  principles  of  surgery  in 
the  Rush  Medical  College,  Chicago,  whose  writings 
have  obtained  a  wide  circulation  and  whose  influence 
in  the  North  and  West  perhaps  transcends  that  of  any 
other  surgeon,  states  in  his  "  Principles  of  Surgery" 
that  inflammation,  in  the  widest  and  most  comprehen- 
sive meaning  of  the  word,  should  be  made  to  embrace 
pathological  conditions  which  are  caused  by  the  action 
of  pathogenic  microbes  or  their  ptomaines  upon  the 
histological  elements  of  the  blood  and  fixed-tissue 
cells,  and  that  "  true  inflammation  is  always  caused  by 
the  presence  of  one  or  more  kinds  of  pathogenic  mi- 
crobes," a  statement  which,  it  may  be  added  in  paren- 
thesis, does  not  prevent  him  from  employing  figures 
from  Hamilton  and  others  to  illustrate  the  stages  of 
the  process,  although  those  figures  represent  the  re- 
sults obtained  by  the  use  of  chemical  and  not  bacte- 
rial irritants. 

Dr.  Roswell  Park,  professor  of  surgery  in  the  Uni- 
versity of  Buffalo,  in  a  straightforward  address  read 
before  the  American  Surgical  Association  in  May  of 
last  year  '  is  inclined  toward  the  same  opinion,  and,  as 
he  at  the  onset  especially  invites  kindly  criticism,  I 
'  Mp:dical  Ri'XORi),  New  York,  i.,  1895,  p.  705. 


lO 


may  say  that  his  challenge  has  perhaps  more  than 
anything  else  led  me  to  take  up  the  subject  here.  He 
urges  first  the  revolutionary  thesis  that  the  combina- 
tion of  the  four  cardinal  symptoms  should  not  be  re- 
garded as  indicating  inflammation.  We  should  dis- 
miss from  our  minds  the  associated  idea,  and  should 
refer  to  the  redness  and  heat  as  hyperaemia,  the  swell- 
ing as  exudation,  the  pain  as  the  result  of  pressure. 
Only  when  these  become  developed  or  modified  by 
the  growth  of  micro-organisms  in  an  injured  area  or 
by  the  action  of  their  products  should  we  venture  to 
speak  of  inflammation.  And  the  term  should  then 
comprise  not  only  the  local  but  also  the  general  effects 
produced  by  the  growth  of  the  micro-organism.  In 
fact,  the  existence  of  these  general  effects  (as,  for  ex- 
ample, the  rise  of  bodily  temperature  associated  with 
the  appearance  of  a  small  furuncle  upon  the  nose)  is 
given  as  a  distinction  between  what  Dr.  Park  regards 
as  true  inflammation  and  the  non-inflammatory  reac- 
tions of  the  tissues  to  non-microbic  lesions. 

While  epitomizing  Dr.  Roswell  Park's  argument,  I 
believe  that  I  have  accurately  stated  his  main  con- 
tentions. 

Let  us  see  what  is  the  logical  outcome  of  this  idea. 
First  and  foremost  the  frequent  association  of  redness, 
swelling,  heat,  and  pain  which  may  result  from  mi- 
crobic  invasions  of  the  body  is  not  in  itself  to  be  re- 
garded as  symptomatic  of  inflammation.  The  associ- 
ation is  common  to  microbic  and  many  other  lesions. 
Only  the  extension  of  this  series  of  symptoms  in 
special  directions  under  the  continued  influence  of 
bacterial  irritation  is  to  be  considered  as  inflamma- 
tory; or,  to  carry  this  view  to  its  logical  conclusion, 
the  surgeon  must  no  longer  depend  upon  the  presence 
of  cardinal  symptoms;  he  must  only  call  a  region  in- 
flamed when  he  has  either  personally  or  through  a 
bacteriologist  determined  the  existence  of  bacteria 
therein.     There  is  no  attempt  made  by  Dr.  Roswell 


1 1 


Park  to  limit  inflammation  to  pyogenvjsis,  and  while 
this  view  of  inflammation  for  surgical  purposes,  in 
the  main,  undoubtedly  separates  suppurative  from 
other  lesions,  it  is  in  the  terms  of  this  definition  im- 
possible to  regard  suppuration  in  itself  as  an  inflam- 
matory manifestation,  simply  because,  as  is  well 
known,  suppuration  may  be  induced  by  caustics  and 
severe  chemical  and  physical  irritants,  apart  from  the 
action  of  bacteria.  As  above  stated,  the  bacteriologi- 
cal is  to  become  the  sole  sufficient  test  of  inflamma- 
tion. While  it  is  true  that  the  general  adoption  of 
this  view  would  result  in  rendering  it  absolutely  neces- 
sary that  every  general  practitioner  should  continually 
practise  himself  in  elementary  bacteriology,  or  else 
should  banish  the  term  inflammation  from  his  diag- 
nostic vocabulary — a  not  undesirable  consummation, 
it  may  be — I  cannot  but  fear  that  the  general  practi- 
tioner will  still  continue  to  speak  of  the  inflammation 
of  scalded  surfaces,  of  black  eyes,  and  of  fractured 
limbs;  for  he  will  still  require  some  useful  and  gen- 
erally accepted  term  to  embrace  the  train  of  symptoms 
following  upon  every-day  injuries.  This  attempt  on 
the  part  of  members  of  one  branch  of  our  profession 
to  delimit  our  idea  of  inflammation  largely  for  practi- 
cal purposes  must  fail  when  put  into  practice. 

Or  let  us  examine  the  proposal  from  another  side. 
"Without  infection,"  says  Dr.  Roswell  Park,  "no 
genuine  inflammation;  with  infection,  inflammation 
and,  what  always  goes  with  conflagration,  more  or  less 
destruction.  Congestion  and  exudation  provoke  little, 
ordinarily  no  constitutional  symptoms;  inflammation 
always  does.  ...  I  would,"  he  states  later  (after 
discussing  hypera^mia,  congestion,  and  "  cirrhotic" 
changes)  "  in  an  entirely  distinct  chapter  and  in  an 
unmistakably  separate  way,  take  up  the  matter  of  in- 
flammation— />.,  infection."  To  all  intents  and  pur- 
poses Dr.  Roswell  Park  would  substitute  a  word 
which,  I  think  most  will  agree,  has  wisely  been  re- 


12 


s^''ictecl  to  local  disturbances  for  a  word  which  has 
snown  itself  most  useful  as  indicating  the  changes 
which  may  occur  in  the  organism  at  large  in  conse- 
quence of  microbic  invasion.  Up  to  the  present  time 
inflammation  has  been  understood  to  indicate  the  local 
changes  following  upon  an  injury;  fever  and  infection 
to  indicate  the  more  remote  effects  upon  the  organism 
at  large.  And  I  am  forced  to  point  out  to  Dr.  Ros- 
well  Park  that  in  ''  infection"  he  has  a  most  useful  word 
which  will  indicate  everything  that  he  wishes  to  in- 
clude in  his  restricted  idea  of  inflammation,  and,  that 
being  so,  there  can  be  no  valid  reason  why  he  should, 
with  those  "big,  merciless  hands"  attributed  by  the 
late  poet  laureate  to  one  of  our  surgical  brethren,  ap- 
propriate a  word  to  which  can  be  given  a  wdder  and  at 
the  same  time  a  more  exact  use.  The  terms  "  wound 
infection,"  "  local  infection"  and  '*  general  infection," 
and  "  infective  inflammation,"  are  in  common  and  sat- 
isfactory employment  and  there  can  be  little  or  no 
doubt  as  to  their  meaning.  I  beg  Dr.  Park  to  con- 
sider this  before  urging  further  the  adoption  of  his 
proposals. 

But  while  one  is  only  too  glad  to  have  a  word  "  in- 
fection" capable  of  covering  the  series  of  local  and 
general  effects  induced  by  the  presence  and  growth  of 
micro-organisms  within  the  body,  its  employment  in 
nowise  tells  upon  the  fact  that  every  change  in  the 
blood  elements  and  tissues  brought  about  by  microbes 
and  their  products  may  be  induced  by  irritants  of  an- 
other nature.  While  it  is  true  that  micro-organisms 
frequently  lead  to  pus  production  and  that  suppurative 
inflammation  is  almost  entirely  induced  by  these 
agents,  it  is  equally  true,  as  was  first  clearly  proved 
by  Councilman,  that  sundry  chemical  substances  can 
occasionally  set  up  an  identical  process.  And  as  Leber 
has  shown,  the  purulent  fluid  produced  by  this  latter 
means  has  definite  powers  of  breaking  up  and  digest- 
ing proteid  matter;  no  clear  distinction  can  be  made 


13 


has 


between  the  septic  and  the  aseptic  pus  save  that  the 
one  is  of  microbic  origin,  the  other  not.  A  broad 
idea  of  inflammation  to  include  all  like  processes 
throughout  the  higher  animals  must  take  cognizance 
of  these  facts. 

Nor  again,  may  I  add,  is  it  possible  to  distinguish 
one  series  of  micro-organisms  as  essentially  pyogenic. 
To  attempt  this  is  to  draw  a  line  between  human  and 
comparative  pathology.  While  it  is  true  that  certain 
forms  in  man  are  peculiarly  liable  to  induce  abscess 
formation,  those  same  forms  by  no  means  necessarily 
exhibit  the  same  liability  in  other  animals,  and  even 
in  man  they  do  not  always  lead  to  pus  formation ;  in 
short,  suppuration  is  the  expression,  not  of  the  pres- 
ence of  certain  specitip  microbe*},  but  of  a  definite 
grade  of  intensity  of  irritation,  or,  in  other  words,  it  is 
a  phenomenon  representing  a  certain  ratio  between 
the  virulence  of  the  irritant  and  the  resisting  powers 
of  the  organism.  Increase  the  virulence  of  a  micro- 
organism or  diminish  the  resisting  power  of  the  or- 
ganism, and  in  members  of  the  same  species  similarly 
treated  we  may  have  every  grade  of  acute  inflamma- 
tion, from  local  hyperremia  and  slight  diapedesis  of 
leucocytes  through  local  abscess  formation,  to  spread- 
ing sero-purulent  cellulitis  and  general  septicaemic 
infection.  Much  has  been  done  experimentally  to 
prove  the  truth  of  this  statement,  while  the  recent 
work  in  the  laboratories  of  this  continent  upon  cases 
of  typhoid  and  gonorrhoea  has  abundantly  shown  how 
micro-organisms  which  in  ordinary  are  not  pyogenic 
can  be  the  prime  causes  of  abscess  formation.  Indeed 
it  may  be  said  with  some  truth  that  the  main  bacte- 
riological work  of  the  past  year  has  been  in  the  direc- 
tion of  confirming  this  statement  and  in  demonstrat- 
ing in  case  after  case  this  liability  on  the  part  of 
bacteria  ordinarily  non-pyogenic  to  lead  to  abscess 
formation. 

If  this  be  so  and  if  bacteria  can  thus  be  the  cause 


14 


of  a  series  of  reactive  changes  on  the  part  of  the  tis- 
sues, advancing  by  imperceptible  gradations  from  the 
simplest  transient  local  inflammatory  change  up  to  the 
most  profound  generalized  septiceemic  disturbance, 
and  if  again,  as  all  must  admit,  they  can  induce  either 
profound  local  destruction  of  tissues  or  well-marked 
local  tissue  overgrowth,  then  surely  it  is  impossible  to 
to  separate  the  lesions  produced  by  micro-organisms 
from  the  parallel  and  identical  series  capable  of  being 
produced  by  other  noxce. 

I  trust,  therefore,  that  I  have  made  it  clear  that  we 
are  compelled  to  range  together  the  series  of  changes 
induced  locally  in  the  tissues  as  the  result  of  injury 
under  the  common  heading  of  inflammation,  and  this 
irrespective  of  the  nature  of  the  irritant. 

For  pathologists  in  general,  for  those  studying  not 
merely  gross  anatomical  lesions  but  finer  also,  for 
those  dealing  with  lesions  of  internal  organs  as  well 
as  with  lesions  having  an  outward  manifestation,  for 
those  whose  pathology  and  study  of  medicine  is  not 
confined  to  man  and  who  strive  to  base  their  knowl- 
edge of  disease  and  its  processes  upon  a  study  of  the 
same  throughout  the  animal  kingdom,  no  other  course 
is  open  and  practical. 

Following  this  train  of  thought  it  becomes  evident 
that  we  must  regard  as  of  inflammatory  origin  all  those 
changes  in  the  tissues  which  we  can  prove  to  result 
from  direct  injury  to  those  tissues,  whatever  the  na- 
ture of  the  irritant,  and  which  we  can  regard  as  tend- 
ing toward  repair.  We  can  separate  the  various 
degenerations  of  the  tissues,  for  these  form  a  well-de- 
fined series  of  changes  from  the  inflammatory  lesions 
proper;  we  may  regard  them  as  associated  with  but 
not  inherent  in  the  inflammatory  change. 

Of  these  local  attempts  at  repair  the  most  durable 
and,  when  the  process  has  come  to  an  end  or  when, 
being  of  moderate  intensity,  it  has  continued  for  some 
little  period,  the   most  evident  is   the   formation   of 


15 


fibrous  tissue.  Now,  in  studying  this  formation  and 
the  broader  subject  of  fibrosis '  in  general,  the  first 
point  to  be  settled,  one  which  will  materially  affect 
our  whole  comprehension  and  classification  of  the 
fibroses,  is  whether  it  is  possible  to  distinguish  be- 
tween new  connective-tissue  formation  which  is  di- 
rectly the  result  of  injury  and  that  which  is  indi- 
rectly the  result,  and  if  we  can  determine  this  we  can 
with  greater  freedom  attack  the  question  of  the  classi- 
fication of  the  fibroses  in  general  and  can  more  surely 
state  which  of  them  are  to  be  considered  of  inflamma- 
tory origin  and  constituting  chronic  "  -itides,"  which 
non-inflammatory. 

The  first  question  is  one  of  peculiar  difficulty,  and 
the  problem  presented  for  solution  may  perhaps  be 
best  approached  by  a  consideration  of  two  widely 
separated  cases.  A  study  of  the  various  stages  of  the 
development  of  a  tubercle  demonstrates  that  in  man 
and  most  mammals  the  first  result  of  the  lodgment  and 
growth  of  the  tubercle  bacilli  in  the  tissues  is  to  stim- 
ulate tissue  formation.  Only  at  a  later  period,  with 
continued  action  of  the  products  of  the  germs  and  as- 
sociated disturbed  nutrition  of  the  central  area  of  the 
granuloma,  does  tissue  destruction  become  manifest. 
There  is  perhaps  no  better  demonstration  than  this, 
unless  it  be  that  afforded  by  lepra  nodules,  of  injury 
leading  directly  to  connective-tissue  growth. 

On  the  other  hand,  we  may  consider  the  processes 
which  occur  in  the  central  nervous  system  following 
upon    atrophy  and  destruction  of   ganglion    cells  or 

'  Here  let  me  state  that  I  have  no  liking  for  this  mongrel  term 
"  fibrosis  "  ;  nevertheless,  I  know  of  none  which  can  satisfactorily 
replace  it.  The  terms  ' '  sclerosis  "  and  "  cirrhosis  "indicate  only 
the  secondary  consequences  of  fibroid  overgrowth,  and  "  fibrous 
hyperplasia"  is  a  little  clumsy,  while  "fibrosis"  undoubtedly 
conveys  clearly  its  meaning;  and  in  its  favor  (although  two  blacks 
do  not  make  one  white)  it  may  be  urged  that  in  common  usage 
we  have  such  other  mongrel  terms  as  *'  fibroma,"  "  fibro-enchon- 
droma,"  and  so  on. 


i6 


I 


in 

!i 


ii 


upon  separation  of  axis-cylinder  processes  from  their 
trophic  nerve  cells.  The  results  can  best  be  seen 
when  the  injury  affects  secondarily  all  the  members 
of  an  ascending  or  descending  tract,  and  they  are  to 
be  summed  up  as  consisting  of  degeneration  of  the 
fibres  forming  the  tract  with  replacement  by  fibrous 
tissue.  Here  there  has  been  no  irritant  circulating  in 
the  lymph  bathing  the  fibres  and  leading  directly  by 
its  action  to  their  destruction.  The  degeneration  and 
atrophy  has  followed  upon  injury  inflicted  at  a  dis- 
tance, an  injury  to  another  region  of  the  body.  If  any 
irritant  be  present  it  is  of  intrinsic  origin.  All  the 
same,  we  see  that  the  atrophied  fibres  become  replaced 
by  connective  tissue. 

Are  we  to  regard  this  "  replacement*'  fibrosis  as  a 
form  of  chronic  inflammation.-*  Against  so  regarding 
it  it  can  be  argued  that,  as  already  stated,  no  specific 
irritant  of  external  origin  can  be  adduced  as  having 
acted  upon  the  tract  of  degeneration,  and  that  in  case 
after  case  where  the  degeneration  has  been  gradual 
none  of  the  ordinary  symptoms  of  inflammation  are 
recognizable,  neither  the  coarser  conditions  of  hyper- 
nemia  and  exudation  nor  those  finer  ones  of  determi- 
nation of  leucocytes  (though  this  phenomenon  is  at 
times  quite  distinct),  multiplication  of  capillaries  and 
other  microscopical  evidences  of  removal  of  destroyed 
tissue,  and  active  new  growth.  Almost  imperceptibly 
the  atrophied  nerve  fibres  are  replaced  by  connective 
tissue,  and  it  may  be  that  of  all  the  accompaniments 
of  ordinary  inflammation  the  sole  distinguishable  is 
the  "functio  la^sa." 

But  there  is  another  aspect  of  the  condition  that  we 
are  forced  to  regard,  and  I  may  best  approach  this  in- 
directly. What  satisfactory  distinction,  it  may  with 
justice  be  asked,  can  be  drawn  between  this  more  in- 
sidious replacement  fibrosis  and  the  grosser  replace- 
ment occurring  in  the  case  of  infarcts?  In  the  latter 
the  normal  course  of  events   is,  that,  infective  agents 


17 


as  a 


being  absent,  the  necrosed  area  becomes  surrounded 
by  a  zone  of  hyperaimia,  the  dead  tissue  undergoes 
disintegration  and  absorption  and  is  replaced  by  new 
fibrous  tissue.  In  such  a  case,  it  is  true,  we  can  rec- 
ognize the  distended  peripheral  vessels,  the  invasion 
by  leucocytes,  the  formation  of  new  vessels,  all  the 
main  microscopical  and  most  of  the  macroscopical 
signs  of  inflammation.  But,  as  in  our  previous  exam- 
ple, no  extrinsic  agent  has  set  up  the  disturbances. 
It  is  difficult,  indeed  impossible,  to  arrive  at  any  other 
conclusion  than  that  the  products  of  necrosis  act  as 
the  irritant  and  that  they  must  be  regarded  as  the 
cause  of  the  inflammation  and  subsequent  fibrous-tis- 
sue development.  It  is  competent  for  us  to  assume 
the  existence  of  a  cryptic  inflammation  in  the  former 
case,  and  to  hold  that  a  like  cause,  namely,  tissue  ne- 
crosis, has  led  to  a  like  effect,  namely,  fibrosis.  And 
indeed  if  we  adhere  to  the  definition  of  inflammation 
that  I  have  laid  down,  both  of  these  cases  of  replace- 
ment fibrosis  so  obviously  represent  the  local  attempts 
at  repair  following  upon  injury  to  the  tissues,  that 
unless  we  further  define  what  is  meant  by  injury 
we  are  forced  to  regard  them  as  equally  of  inflammatory 
origin. 

We  see  thus  that  two  different  types  of  fibrous-tis- 
sue development,  one  hyperplastic,  the  other,  as  I  have 
termed  it,  replacement,  may  be  of  inflammatory  origin, 
and  the  more  one  examines  into  the  subject  the  more 
difficult  is  it  found  to  recognize  inflammatory  fibroses 
by  their  histological  characters.  While  it  is  true  that 
in  certain  cases  we  have  histological  evidence  of  pro- 
gressive inflammation — the  presence  of  newly  formed 
vessels,  of  an  increased  number  of  extravascular  leu- 
cocytes and  small  round  cells,  and  it  may  be  of  a  cer- 
tain amount  of  exudation — in  cases  of  the  same  nature 
at  a  later  date  all  these  signs  may  be  wanting,  and 
again,  in  other  allied  cases,  from  the  very  onset  both 
microscopical  and  macroscopical  indications  of  inflam- 


i8 


miition  may  l)c  peculiarly  rare.  We  cannot  depend 
upon  hisloloj^ical  evidence  alone.  At  the  most 
we  can  classify  the  various  forms  according  to  the 
evidence  in  our  possession  as  to  their  origin  and 
tendencies. 

The  considerations  I  have  brought  forward  up  to 
this  point  would  lead  us  to  distinguish  at  least  two 
main  types  of  fibroid  change  associated  with  inflam- 
mation, one  of  which  in  default  of  a  better  name  may  be 
termed  productive,  the  other  replacement,  fibrosis.  In 
the  former  there  is  no  causal  relationship  between  the 
amount  of  new  connective  tissue  resulting  from  the 
inflammatory  action  and  the  amount  of  tissue  dis- 
placed; in  the  latter  the  amount  of  new  fibrous  tissue 
developed  appears  to  be  primarily  governed  by  and 
proportioned  to  the  extent  of  the  destructive  process, 
but  both  equally  tend  toward  repair  and  arrest  of  in- 
jury. 

This  division  will,  I  think,  be  found  useful,  and  it 
will  be  seen  that  the  leading  forms  of  inflammatory 
fibroid  change  are  to  be  grouped  under  one  or  other  of 
these  heads. 

Under  the  first  are  to  be  included  sundry  localized 
fibroses  of  which  the  main  forms  are  the  focal  areas  of 
new  connective-tissue  growth  induced  by  the  presence 
of  certain  micro-organisms,  that  is  to  say,  the  more 
chronic  or  less  acute  forms  of  infective  granulomata — 
the  new  growths  (tubercles)  induced  by  the  tubercle 
bacilli,  those  (gummata)  induced  by  the  not  surely 
determined  organism  of  syphilis,  the  fibroid  nodules 
caused  by  the  presence  of  the  leprosy  bacilli,  and,  again, 
the  more  chronic  type  of  actinomycotic  and  glanders 
lesions.  Examples  are  not  wanting  of  similar  focal 
areas  of  fibroid  growth  induced  by  simple  irritation. 
As  such  may,  I  think,  be  safely  cited  the  earliest  stage 
tof  one  form  of  cheloid.  Although,  as  I  shall  point  out 
later,  cheloid  growths  must  be  included  among  the 
fibromata,  nevertheless,  in  many  cases  of  what  is  some- 


'9 


4 


xr. 


times  termed  and  rejijarded  as  spontaneous  cheloid, 
localized  connective-tissue  growths  can  L<^  excited  by 
local  irritation  of  the  sui fj-^e.  Mils  was  well  ob- 
served in  a  case  which  has  recently  been  very  fully 
studied  by  one  of  my  students,  Mr.  K.  H.  Martin.  In 
this,  the  mere  scratching  with  a  pin  was  sufficient  to 
give  rise  to  the  new  growth.  I  am  myself  fullv  pre- 
pared to  regard  sundry  cases  of  focal  growth  as  non- 
inflammatory— as  due  to  stimulation  rather  than  to  in- 
jury. The  difficulty  is  that  there  is  no  line  separating 
the  one  from  the  otiier;  there  is  no  sharply  defined 
boundary  between  simple  hyperplasia  and  that  which 
is  obviously  reparative. 

Merging  at  times  imperceptibly  into  the  previous 
group  there  are  the  capsular  fibroses,  comprising 
those  cases  of  connective-tissue  development  induced 
around  an  irritant,  whether  infective  or  not.  Here 
the  zone  or  capsule  of  tissue  formation  is  a  develop- 
ment of  so  much  new  material,  laid  down,  it  would 
seem,  irrespective  of  previous  tissue  destruction  in  the 
immediate  region  of  its  appearance.  Examples  of 
this  form  will  be  immediately  called  to  mind.  Among 
the  infective  we  have  the  thick  capsules  forming 
around  obsolescent  tuberculous  masses,  around  chronic 
abscesses  and  phthisical  cavities;  among  the  simple 
irritative  are  to  be  classed  the  capsules  developed 
around  such  foreign  bodies  as  exercise  little  more 
than  a  mechanical  irritation,  whether  those  bodies  be 
solitary  and  of  large  size,  as,  for  example,  impacted 
bullets,  or  minute  and  very  numerous,  as  inhaled 
particles  of  coaly  or  silicious  matter.  Whether  the 
capsules  formed  around  and  merging  into  the  frame- 
work of  benign  tumors  are  to  be  classed  as  of  simple 
irritative  or  of  infective  origin  may  possibly  give  rise 
to  debate;  provisionally  I  must  refer  them  to  the 
former  class. 

Another  type  of  productive  fibrosis,  one  that  can- 
not satisfactorily   be  classed  either    as    localized   or 


20 


iiiii 


'1 


generalized,  is  that  due  to  inflammation  of  serous 
surfaces,  a  form  including  the  fibroid  thickening  of 
serous  superficies  and  organized  inflammatory  ad- 
hesions. 

Besides  these,  there  exist  also  generalized  produc- 
tive fibroses  of  inflammatory  origin,  which  again  may 
either  be  of  infective  origin  (induced  by  bacteria  or 
their  products)  or  the  result  of  continued  non-infec- 
tive irritation.  The  chronic  interstitial  pneumonia 
following  upon  subacute  pleurisy  may  be  cited  among 
the  former;  among  the  latter,  in  all  probability,  the 
generalized  interstitial  fibrosis  of  so-called  chronic 
parenchymatous  disease,  of  which  a  good  example  is 
afforded  by  the  condition  of  productive  parenchymatous 
nephritis.  But,  as  I  shall  have  later  occasion  to  point 
out,  some  forms  at  least  of  interstitial  fibrous  over- 
growth are  rather  to  be  counted  among  the  replacement 
than  among  the  productive  forms. 

The  local  and  general  forms  may  merge,  the  one 
into  the  other.  Thus,  a  liver  presenting  gummata 
may  exhibit  also  well-marked  generalized  interstitial 
fibroid  overgrowth;  a  kidney  the  seat  of  chronic  tuber- 
culosis may  show  the  same;  or  again,  in  the  inhalation 
pneumonias  the  deposit  of  foreign  particles  along  the 
lymph  spaces  of  the  lungs  may  be  so  extensive  and 
the  growth  thereby  excited  be  so  great  that  the  organs 
present  the  characters  of  a  generalized  interstitial  in- 
flammation. Nevertheless,  the  distinction  between 
local  and  general  is  in  the  main  useful  and  not 
pedantic. 

To  turn  now  to  the  replacement  fibroses;  among 
these  we  can  distinguish  certain  well-defined  types. 
All  may  in  truth  be  termed  cicatricial,  but  it  may  be 
well  to  restrict  this  designation  to  the  ordinary  surgi- 
cal cicatrix,  to  the  connective  tissue  developed  after 
breach  of  continuity  in  a  part.  Speaking  broadly,  it 
may  be  said  that  every  such  breach  of  continuity  re- 
sults in  the  destruction  of  a  certain  number  of  cells. 


^ 


.1  ! 


21 


serous 
ning  of 
)ry    ad- 

produc- 

in  may 

eria  or 

n-infec- 

;umonia 

1  among 

lity,  the 

chronic 

mple  is 

ymatons 

to  point 

as  over- 

acement 

the  one 
^ummata 
terstitial 
ic  tuber- 
halation 
long  the 
live  and 
s  organs 
itial  in- 
between 
and   not 

among 
d  types, 
may  be 
■y  surgi- 
ed  after 
Dadly.  it 
luity  re- 
)f  cells, 


and  that  in  the  absence  of  infective  agents  the  new 
connective-tissue  formation  maintains  a  definite  rela- 
tionship to  the  amount  of  previous  destruction,  never 
exceeding  it.  Very  closely  allied  is  the  development 
following  upon  the  complete  and  sudden  necrosis  of 
all  the  elements  of  a  tissue;  of  this,  as  previously 
hinted,  a  most  satisfactory  example  is  seen  in  the  heal- 
ing of  a  simple  infarct. 

If  we,  following  what  is  not  unusual  nowadays,  re- 
gard the  blood  as  a  tissue,  the  organization  of  thrombi 
must  be  placed  under  the  same  heading  of  fibrosis  fol- 
lowing tissue  necrosis;  if  we  are  more  conservative  in 
our  employment  of  the  term  "  tissue,"  we  must  regard 
the  gradual  substitution  of  the  coagulated  and  ne- 
crosed blood  by  fibrous  tissue  as  a  closely  allied  phe- 
nomenon, namely  as  a  fibrosis  occurring  in  and  re- 
placing a  necrotic  mass. 

Associated  with  these  we  can  recognize  two  other 
forms.  I  would  not  insist  upon  their  separation,  but 
there  is  a  slight  difference  in  their  mode  of  origin. 
In  the  one  the  essential  cause  of  the  death  of  the 
cells  is  local,  from  impaired  nutrition,  in  the  other 
the  nobler  elements  of  the  tissue  undergo  atrophy 
and  death  irrespective  of  local  conditions.  The 
two  forms  may  be  termed  dystrophic  and  atrophic 
respectively. 

Of  the  atrophic  I  have  already  furnished  an  exam- 
ple, namely,  the  sclerosis  following  degeneration  of 
ascending  or  descending  nerve  tracts.  Of  the  dys- 
trophic the  heart  furnishes  the  most  frequent  exam- 
ples, though  I  am  inclined  to  regard  much  of  the 
fibroid  change  seen  in  the  senile  kidney  as  of  the 
same  nature.  As  M.  H.  Martin  '  was,  I  think,  the 
first  to  point  out  explicitly,  and  as  Weber'"  has  shown 
in  a  very  careful  research,  where  there  is  an  "obliter- 

'  II.  Martin:  Kevue  de  Medecine,  May,  iS8i. 
-  A.  Weber:  "  Contributioii  a  I'Etude  Anatomo-patholoj^iciue  de 
rArterio-sclerose  du  Coeur,"  Paris,  Steinheil,  1887. 


2  2 


m 


ating  endarteritis"  of  the  coronary  vessels  with  over- 
growth of  the  intima  and  consequent  diminution  of 
the  lumen,  there  must  result  a  diminished  nutrition  of 
the  area  supplied  by  each  affected  artery  or  arteriole, 
and  as  these  are  of  the  nature  of  end  arteries  there  is 
developed  no  satisfactory  collateral  nutrition.  The 
result  affords  a  very  striking  picture,  more  especially 
if  the  most  frequent  seat  of  the  change  be  examined, 
namely,  one  of  the  papillary  muscles  of  the  left  heart. 
In  these  the  fibres  run  longitudinally  and  so  also,  en- 
tering at  the  base,  do  the  nutrient  arteries,  and  the 
condition  is  so  common  that  I  have  never  had  diffi- 
culty in  obtaining  material  for  my  class  in  morbid 
histology.  In  a  typical  fairly  advanced  case  in  trans- 
verse section  of  the  muscle,  the  arterioles  with  thick- 
ened intima  are  seen  cut  transversely;  around  each 
is  a  zone  of  fairly  healthy  fibres  also  cut  transversely. 
Passing  outward  from  the  artery  these  give  place  to 
fibres  that  present  atrophy  and  pigmental  degenera- 
tion with  intermingling  of  new  connective  tissue, 
while  the  outer  zone  of  supply  of  the  arteriole  is  rep- 
resented by  a  ring  of  clear,  transparent  fibrous  tissue 
with  relatively  few  nuclei  and  here  and  there  the  last 
remnant  of  a  degenerated  muscle  fibre.  This,  I  may 
remark,  is  but  one  form  of  cardiac  sclerosis.  It 
would  be  difficult  to  find  a  more  demonstrative  case 
of  this  dystrophic  replacement  fibrosis. 

But  while  thus  we  are  able  to  recognize  examples 
of  the  uncomplicated  occurrence  of  one  or  other  form 
of  inflammatory  fibrosis,  and  while  I  hold  that  it  is 
useful  to  us  both  as  students  of  medical  science  and 
as  practical  physicians  and  surgeons  to  seek  to  ana- 
lyze the  nature  and  character  of  every  morbid  change, 
it  has  to  be  admitted,  if  we  look  honestly  at  things  as 
they  are,  that  case  after  case  presenting  itself  to  our 
notice  cannot  possibly  be  docketed  and  pigeonholed 
under  one  heading.  Time  and  again  we  come  across 
what  can   only  be   classified  as  mixed  forms  of   the 


i 


23 


^ 


conditions  already  indicated,  not  to  mention  mixture 
of  these  with  fibroid  conditions  which  I  have  still  to 
take  into  consideration.  I  can  only  urge  that  it  is 
well  to  strive  to  cultivate  our  garden  and  not  to  allow 
our  ideas  of  chronic  inflammation  to  continue  a  riot- 
ous and  tangled  growth.  Only  by  such  cultivation 
can  we  hope  to  gain  good  fruit. 

It  is  when  we  come  to  study  the  chronic  inflamma- 
tions affecting  glandular  organs  that  our  great  diffi- 
culty begins  in  comprehending  the  essential  nature 
and  causation  of  connective-tissue  growth.  Let  us 
take  the  commonest  case,  namely,  that  of  continued 
parenchymatous  inflammation.  Here  the  first  obvious 
disturbance  in  the  tissue  is  an  affection  of  the  glan- 
dular cells.  With  this  there  is  an  accompanying  con- 
gestion of  the  interstitial  vessels,  and  this  gives  place 
eventually  to  a  condition  in  which  the  collections  of 
gland  cells  are  separated  from  each  other  by  increased 
connective  tissue,  while  coincidently  the  gland  cells 
themselves  show  signs  of  atrophy.  Two  conditions 
might  produce  this  picture:  either  the  atrophy  of  the 
gland  cells  might  be  primary  and  the  increased  fibrous 
tissue  an  indication  of  replacement  fibrosis;  or,  on 
the  other  hand,  the  picture  might  indicate,  as  is  usually 
held,  a  productive  interstitial  fibrosis  with  the  malnu- 
trition and  atrophy  of  the  gland  cells  as  a  secondary 
consequence  of  irritation,  impaired  nutrition,  and 
pressure  exerted  by  the  new-formed  tissue  combined. 
It  is  only  by  a  very  full  and  cautious  observation  that 
it  is  possible  to  arrive  at  a  decision  in  any  given  case 
as  to  which  form  of  fibrosis  is  represented  and  often, 
indeed,  one  is  induced  to  take  the  middle  course  and 
consider  both  in  operation. 

If,  for  example,  we  study  the  various  forms  of  cir- 
rhosis of  the  liver,  both  experimentally  and  by  histo- 
logical examination  of  various  cases,  this  difficulty  is 
very  forcibly  borne  home  to  us.  We  can  occasionally, 
it  is  true,  make  out  with  certainty  the  existence  of  a 


24 


■«■ 


productive  fibrosis;  thus  we  frequently  meet  with 
what  appears  to  be  the  earliest  stage  of  ordinary  so- 
called  alcoholic  cirrhosis,  in  which  we  observe  small 
masses  of  small-celled  infiltration  along  the  portal 
sheaths.  The  condition  looks  definitely  productive; 
it  appears  to  be  an  inflammation  around  the  interlobu- 
lar branches  of  the  portal  vein,  and  the  cells  in  the 
immediate  neighborhood  of  these  accumulations  show 
no  very  decided  signs  of  degeneration  and  atrophy. 
We  can,  again,  as  is  occasionally  the  case  in  early 
stages  of  biliary  obstruction,  find  the  bile  ducts  en- 
larged and  dilated  and  surrounded  each  with  new  con- 
nective tissue,  so  that  the  picture  given  is  that  of  a 
productive  inflammation  immediately  around  these 
ducts.  We  can  also,  more  frequently  than  is  usually 
recognized,  make  out  signs  of  fibrous-tissue  over- 
growth around  the  branches  of  the  hepatic  artery ;  out 
of  eighty-eight  post-mortems  performed  during  last 
year,  I  found  this  periarteritis  to  be  well  marked  in 
six  cases;  but  in  advanced  cases  of  ordinary  cirrhosis 
of  the  atrophic  type  it  seems  to  me  more  than  doubt- 
ful whether  malnutrition  of  the  cells  does  not  become 
an  important  factor  and  their  atrophy  be  not  followed 
by  replacement  fibrosis,  rather  than  be  the  result  of 
pressure  and  encroachment  of  the  newly  developed 
connective  tissue. 

In  this  connection  it  is  interesting  to  note  how  the 
majority  of  observers  who  have  attempted  experi- 
mentally to  induce  cirrhosis  of  the  liver  have  noticed 
changes  of  a  degenerative  character  in  the  hepatic 
cells  as  a  first  effect  of  irritation  rather  than  produc- 
tive inflammation  in  the  interstitial  substance.  This, 
of  course,  is  what  might  be  expected,  the  nobler  cells 
of  the  tissue  being  the  more  sensitive.  I  merely  draw 
attention  to  it  because  it  is  so  common  to  regard 
hepatic  cirrhosis  as  primarily  an  interstitial  distur- 
bance. I  do  not  wish  to  give  the  impression  that 
this  may  not  be  so  in  certain  cases ;    very  frequently, 


25 


t   with 
ary  so- 
small 
portal 
Lictive; 
srlobu- 
in  the 
show 
rophy. 
early 
cts  en- 
w  con- 
at  of  a 
these 
isually 
over- 
:y;  out 
ig    last 
keel  in 
rrhosis 
doiibt- 
)ecome 
llowed 
suit  of 
eloped 

ow  the 
ixperi- 
loticed 
lepatic 
roduc- 
This, 
r  cells 
^  draw 
regard 
iistur- 
n  that 
lently, 


I  feel  as  sured,  it  is  not.  I  need  but  remind  you 
how  strongly  the  recent  studies  by  Flexner '  uphold 
this  view. 

Here  I  may  briefly  refer  to  certain  studies  which 
have  occupied  me  during  the  last  two  years  upon  the 
causation  and  nature  of  a  very  remarkable  disease 
affecting  the  cattle  in  a  limited  region  of  Nova  Scotia, 
the  so-called  Pictou  cattle  disease.  I  do  not  wish 
here  to  publish  a  detailed  and  circumstantial  account 
of  my  observations,  for  to  do  so  would  not  be  just  to 
Professor  Welch,  to  whom  I  have  promised  my  com- 
pleted paper  upon  the  subject.  I  may,  however,  re- 
peat what  is  stated  in  my  reports  to  the  Dominion 
government,  namely,  that  the  disease  is  of  an  infec- 
tious nature  and  due  to  a  minute  bacillus,  character- 
ized, as  are  so  many  of  the  pathogenic  micro-organisms 
of  lower  animals,  by  an  intense  polar  staining,  so  that 
frequently  it  has  the  appearance  of  a  diplococcus 
rather  than  of  a  bacillus. 

The  disease  is  apparently  of  slow  onset;  the  affected 
cattle  eventually  suffer  from  an  abundant  dark-colored 
diarrhcea,  present  a  moderate  amount  of  ascites,  fail 
to  give  milk,  and  then  the  end  is  ushered  in  either  by 
a  condition  of  violent  excitement  or  by  progressive 
muscular  weakness. 

At  the  post-mortem  the  most  characteristic  features 
are  the  ascites,  a  remarkable  submucous  oedema  of 
portions  of  the  intestine  (I  have  seen  similar  submu- 
cous cedema  in  cirrhosis  of  the  liver  in  man),  enlarge- 
ment of  the  abdominal  lymphatic  glands,  and  a  very 
extensive  cirrhosis  of  the  liver.  It  is  in  the  lymph 
glands  and  the  hepatic  cells  that  the  bacilli  are  pres- 
ent in  greatest  abundance. 

The  cirrhosis  is  generalized  and  of  the  pericellular 

type,  and  if  the  livers  from  a  large  number  of  cases 

be    examined  the  earliest  stages  would  appear  to  be 

those  of  swelling  and  vacuolation  of  the  hepatic  cells 

M^lexner:   Medical  News  (Phila.) ,  ii.,  1894,  p.  116. 


26 


with  great  irregularity  in  the  size  of  the  nuciei. 
There  may  be  great  congestion  of  the  hepatic  (venous) 
capillaries,  but  this  is  unaccompanied  by  any  notable 
small-celled  infiltration.  Following  upon  this  stage 
of  swelling,  the  hepatic  cells  undergo  atrophy,  sundry 
lobules  and  portions  of  the  liver  showing  the  process 
at  a  more  advanced  stage  than  do  other  portions. 
And  this  process  may  be  so  extensive  that  over  large 
areas  of  the  organ  only  isolated  liver  cells  or  clumps 
of  three  or  four  degenerating  cells  are  to  be  recog- 
nized. With  this  the  organ  is  not  diminished,  in- 
deed the  edges  often  tend  to  be  slightly  rounded  and 
full;  there  is  replacement  of  the  degenerating  cells 
and  lobules  by  a  delicate  somewhat  oedematous  con- 
nective tissue.  A  characteristic  of  this  new  tissue  is 
the  relative  absence  of  the  ordinary  signs  of  produc- 
tive inflammation  in  the  shape  of  small  round  cells. 
Of  these  there  are  a  few,  but  very  few ;  more  frequent 
are  small  irregular  cells,  evidently  degenerated  liver 
cells  and  others  of  the  "  spider-cell"  variety,  with 
fairly  numerous  delicate  processes. 

In  short,  the  impression  gained  by  studying  nu- 
merous sections  obtained  from  many  animals  dying 
in  different  stages  is  that  there  is  here  a  primary  irri- 
tation or  overstimulation  of  the  hepatic  cells  by  the 
bacilli,  followed  by  an  atrophy  of  the  same  and  coin- 
cident replacement  fibrosis.  I  will  not  say  that  this 
replacement  fibrosis  is  the  only  form  of  connective- 
tissue  hyperplasia  present  in  these  cases;  there  are 
occasional  indications  of  productive  change.  But  it 
is,  I  feel  assured,  the  main  form  present. 

This  generalized  pericellular  cirrhosis  is,  of  course, 
not  strictly  comparalDle  with  the  more  usual  foiais  of 
hepatic  cirrhosis  met  w-ith  in  the  human  being.  I:-- 
interest  lies  in  this,  that  occasionally,  more  especially 
in  children,  we  observe  a  curiously  similar  condition 
of  the  liver  without  any  clear  evidence  of  syphilis, 
and  in  children  also  the  victims  of  congenital  syphi- 


li 

S] 

si 
b 
s: 

P 
o 

n 
tl 


stage 


in- 

d  and 

cells 

con- 

sue   is 

roduc- 

cells. 

jquent 

liver 

with 


I:^ 


lis,  even  as  to  a  less  extent  in  adults  presenting  tertiary 
syphilis,  we  are  apt  to  meet  with  a  more  or  less  exten- 
sive pericellular  cirrhosis.  In  such  cases  it  may  well 
be  that  the  cirrhosis  is  of  like  origin,  due,  that  is  to 
say,  to  the  direct  irritation  of  the  hepatic  cells  by 
pathogenic  bacteria  or  their  products,  to  the  atrophy 
of  these  cells  and  their  replacement  by  delicate  con- 
nective tissue. 

Thus  far,  therefore,  we  have  been  able  to  recognize 
the  following  forms  of  fibrosis  of  inflammatory  origin : 


A.    "  I'roductive"  fibroses. 

(i)  Localized   -,      ^     ', 
^  '  /  capsular, 

,  ,  , ,  1       n      •      i  local. 

(2)  Serous    and    adhesive  •  , 
^  '                                          I  general. 

(3)  Interstitial, 

li.    "  Replacement  "  fibroses, 
(i)  Cicatricial. 

(2)  (rost)-necrotic, 

(3)  (]^ost)-alrophic. 

(4)  (I'osti-dystrophic. 
C.    Mixed  fibroses. 

But  this  classification  does  not  nearly  include  all 
the  examples  of  connective-tissue  overgrowth  and  scle- 
rosis occurring  in  the  organs  of  the  body. 

One  further  group  of  cases  may  at  first  sight  appear 
to  be  sharply  defined,  namely,  the  group  of  the  true 
fibroid  neoplasms,  the  fibromata  proper.  Neverthe- 
less, a  study  of  the  forms  usually  included  in  this 
group  reveals  the  fact  that  there  has  been  in  the  past 
not  a  little  confusion  as  to  what  constitutes  a  fibroma, 
and  an  attempt  to  classify  the  various  forms  cannot 
but  lead  to  the  conclusion  that  the  line  separating  in- 
flammatory new  formation  from  fibroid  neoplasms  can 
be  drawn  only  with  a  cautious  hand. 

As  I  have  pointed  out,  one  result  of  irritation  may 
be  overgrowth  of  connective  tissue.  Ordinarily  this 
appears  to  be  not  greatly  in  excess  of  the  needs  of  the 
injured  area,  nevertheless  at  times  it  exhibits   itself 


28 


■ft 

i 


greatly  in  excess  of  these  needs.  When  infective 
agencies  interfere  with  the  normal  course  of  cicatri- 
zation of  a  wound  and  the  healing  becomes  delayed, 
when,  in  short,  superadded  to  the  normal  tendency  for 
fibrous  tissue  to  be  developed  so  as  to  repair  a  wound 
there  is  a  stimulus  to  connective-tissue  proliferation 
from  the  presence  of  b?i:teria  and  their  products,  then 
it  would  appear  that  fibrous  tissue  may  be  developed 
in  excess  of  the  requirements  of  the  part.  This 
"false"  cheloid,  it  is  clear,  originates  primarily  after 
inflammation,  and  we  may  have  every  gradation  from 
what  may  be  regarded  without  second  thought  as  re- 
dundant cicatricial  tissue  up  to  what,  from  its  con- 
tinued and  very  extensive  growth,  it  is  difficult  to  re- 
gard as  other  than  a  frank  neoplasm.  Another  form 
I  have  already  referred  to,  namely,  the  "  spontaneous" 
cheloid  developing  where  there  has  been  no  breach  of 
continuity  of  the  tissues.  On  this  continent  among 
the  colored  population  (and  the  negro  appears  to  be 
peculiarly  prone  to  be  affected)  cases  have  been  re- 
corded in  which  the  new  formation  has  attained  enor- 
mous proportions. 

As  an  example  of  so-called  spontaneous  cheloid  let 
me  here  briefly  describe  the  case  already  referred  to, 
studied  by  Mr.  R.  Martin,  for  it  throws  light  upon 
sundry  important  features  in  this  class  of  tumors. 
The  patient  was  a  French  Canadian  girl,  aged  twenty, 
who  had  always  been  healthy  until  about  four  years 
ago,  when  she  noticed  a  very  small  growth  which 
looked  like  a  little  pimple  on  her  left  shoulder.  This 
gradually  enlarged  and  in  about  a  year  began  to  be 
painful,  causing  sharp,  stinging  pains.  At  the  end  of 
two  years  it  was  two  inches  long  and  three-quarters 
of  an  inch  wide,  and  was  then  removed  by  the  knife. 
About  three  weeks  after  the  operation  it  recurred  and 
became  as  large  as  before.  An  operation  four  months 
later  was  again  follow^ed  by  a  recurrence.  Three  or 
four  months  later  it  was   removed  "■  by  means   of   a 


m^. 


29 


plaster."  It  has  never  returned,  but  there  remains  a 
very  large  cicatrix,  larger  in  fact  than  the  original 
tumor.  The  patient  was  free  from  any  further 
growths  until  about  a  year  ago,  when  another  small 
pimple  appeared  on  the  outer  side  of  the  right  arm 
just  above  the  elbow,  which  gradually  grew  larger 
until  in  April,  1895,  it  was  one  inch  long,  about  a 
third  of  an  inch  wide,  and  elevated  above  the  skin. 
The  edges  where  it  passed  into  the  surrounding  skin 
were  irregular  and  claw-like.  On  further  examination 
another  similar  tumor  was  found  on  the  back,  and 
when  the  skin  was  made  tense  in  several  places,  prin- 
cipally on  the  outer  side  of  the  right  arm,  clusters  of 
flat,  small  round  cicatricial  spots  were  noted,  of  a  white 
and  glistening  appearance.  Each  cluster  contained 
about  four  or  live  spots.  Upon  relaxing  the  skin 
these  clusters  were  unnoticeable.  In  July  the  clus- 
ters had  all  disappeared  and  there  remained  only  the 
tumor  on  the  back,  which  was  also  diminishing  in 
size.  At  this  time  needle  scratches  were  made  on  the 
left  arm.  When  seen  again  in  September,  1895,  little 
nodular  lines  of  cicatricial  aspect  were  to  be  observed 
corresponding  to  the  previous  slight  scratches  caused 
by  the  needle.  It  may  be  added  that  microscopical 
examination  of  the  tumor  removed  from  the  arm  in 
April  presented  all  the  characters  of  true  cheloid. 

Here,  then,  we  have  a  case  apparently  of  sponta- 
neous cheloid,  in  which  nevertheless  the  subsequent 
history,  results  of  operation,  and  of  experimental 
slight  cutaneous  disturbance  show  that  the  fibroid 
hyperplasia  was  to  be  induced  by  injury,  so  that  pre- 
sumably the  primary  growth  had  a  similar  origin,  not 
improbably,  as  in  certain  recorded  cases,  from  an  acne 
pustule.  The  case  affords  an  example  of  what  might 
very  easily  in  its  earlier  stages  have  been  classified 
as  spontaneous  cheloid. 

In  fact,  from  this  case  and  from  a  study  of  the  liter- 
ature of  cheloid,  I  am  led  with  Jonathan  Hutchinson 


;o 


.:;  1 


to  doubt  whether  the  conception  of  a  spontaneous  che- 
loid  is  possible  or  consonant  with  facts. 

Thus,  it  can  be  shown  that  in  those  exhibiting  a  ten- 
dency to  the  disease-  -those  in  whom  cheloid  masses 
already  exist — a  minimal  irritation  as,  for  example, 
the  scratch  of  a  pin,  may  induce  the  subsequent  ap- 
pearance of  a  mass  of  subcutaneous  fibrous  tissue  in 
the  region.  Where  this  is  the  case  it  is  difficult  to 
deny  that  the  condition  originates  as  a  productive  in- 
flammatory fibrosis,  and  the  fact  that  at  times  some  if 
not  all  of  the  multiple  nodules  undergo  absorption 
and  disappear  (as  happened  in  Mr.  Martin's  case  to 
which  I  have  already  referred)  is  against  regarding 
the  condition  as  typically  fibromatous.  It  is  equally 
difficult,  in  fact  impossible,  to  maintain  that  a  mass  oi 
new  tissue,  which  occasionally  attains  to  the  weight 
of  a  pound  or  more,  projecting  from  the  head  or  trunk 
is  an  example  of  inliammatory  fibrosis.  It  is  difficult 
to  see  where  the  line  is  to  be  drawn,  unless,  as  I  have 
recently  urged  in  an  address  before  the  Mcdico-Chi- 
rurgical  Society  at  Montreal,'  we  recognize  that  in 
inrtammation  the  new-tissue  formation  ceases  with  the 
removal  or  cessation  of  the  irritant,  whereas  in  neo- 
plasms the  cells,  having  once  commenced  to  proliferate 
rapidly  (whether  as  the  result  of  chronic  inflamma- 
tion of  moderate  intensity  or  from  other  cause  or 
causes),  gain  a  habit  of  growth  and  continue  to  prolif- 
erate independently  of  any  due  stimulus.  Assuredly, 
in  these  multiple  cheloids  as  in  the  cicatricial  forms 
growth  of  the  tissue  is  continued  after  the  irritant  has 
ceased  to  be  in  evidence,  and  consequently  I  am 
bound  from  their  course  to  classify  them  as  among  the 
fibromata— as  fibromata  of  inflammatory  origin. 

I  am  not  prepared  to  do  the  same  with  another 
form,  the  so-called  "  lamellar  fibromata,"  whereof  the 
most   frequent   examples   are   to    be   encountered    as 

1  "The  Habit  of  Growth,"  Montreal  ^Medical  Journal,  Febru- 
ary, 1896. 


^.I 


clie- 


<lense,  sharply  defined,  whitisli  nodules  and  small 
plaques  upon  the  surface  of  the  spleen.  So  far  as  I 
have  been  able  to  follow  their  development,  these  ap- 
pear to  be  examples  of  pure  and  simple  intlammatory 
jijrowth.  I  can  see  in  them  no  evidence  of  continued 
growth  independent  of  injury  or  irritation. 

l^esides  these  two  forms  we  have  the  group  of  typi- 
cal fibromata,  isolated,  sharply  defined  neoplasms  of 
in  general  slow  growth.  While  among  the  cheloids 
we  can  postulate  an  inHammatory  origin,  in  these  we 
cannot  as  yet  venture  to  assign  a  satisfactory  causa- 
tion. Nor  is  the  time  quite  ripe  to  make  a  positive 
statement  concerning  the  massive  interstitial  tissue 
occurring  in  sundry  mixed  tumors,  in  fibrolipomata, 
fibromyxomata,  scirrhous  cancer,  etc.  Studying  these 
and  comparing  the  outer  border  with  the  more  internal 
parts,  1  gain  the  impression  that  in  many  cases  we 
have,  as  in  cheloid,  to  deal  with  a  productive  inflam- 
matory fibrosis  which  merges  insensibly  into  neoplas- 
tic incontinent  growth.  This  is  my  impression,  and  I 
dare  make  no  more  definite  statement, 

I'luis  we  can  divide  the  forms  contained  under  the 
title  of  fibroma  into: 

A.    I'ure  or  true  f"il)ronia. 

(i)  Of  inllamnialory  orij^in  (most  if  not  all    examples  of 

cheloi<l). 
(2)  Of    undetermined    causation    (typical     hard    and   soft 
tibromata). 
1).    Mixed   tibroma,   beniijn,  cancerous,  and  sarcomatous  (admix- 
ture of  fibroid  overjjrowth  with  over^n^wth  (jf  other  tissues). 
(-".    i'alse  fibroma  (due  to  simple  productive  inflammation,  I'-j^''., 
"lamellar"  libromata). 


32 


LHCTURE  II. 

In  my  last  lecture,  having  laid  down  my  definition  of 
inflammation — namely,  that  it  is  the  series  of  changes 
constituting  the  local  attempt  at  repair  of  injury  or  re- 
ferred injury  to  a  part — I  proceeded  to  discuss  the 
forms  of  fibrous  hyperplasia  which  in  the  terms  of  this 
definition  might  well  be  lield  to  be  of  inflammatory 
origin,  and  showed  or  attempted  to  show  that  such 
forms  might  be  divided  into  the  two  main  classes  of 
productive  and  replacement  fibrosis.  Following  upon 
this,  I  discussed  the  group  of  localized  neoplastic 
fibrous  hyperplasias,  and  pointed  out  that  two  groups 
might  be  recognized:  the  neoplasms  of  inflammatory 
origin  and  those  of  as  yet  undetermined  causation — 
the  true  fibromata. 

A  consideration  of  neoplastic  growth  leads  almost 
insensibly  to  the  inquiry  whether  it  is  requisite  that 
injury  should  precede  new  connective-tissue  formation. 
The  answer  must,  I  think,  be  an  unhesitating  No. 

In  the  nobler  tissues  of  the  body  we  know  full  well 
that  increased  work  leads  to  hypertrophy  or,  more  cor- 
rectly, to  hyperplasia;  that  is  to  say,  a  physiological 
stimulus  leads  to  multiplication  of  the  cell  elements. 
What  are  the  exact  steps  whereby  this  is  brought  about 
must  perhaps  always  remain  a  matter  of  supposition, 
the  most  that  we  can  say  being  that  the  call  for  in- 
creased work  is  followed  by  increased  blood  flow  to 
the  part  with  presumably  increased  nutrition,  and  that 
the  increased  work  necessitates  greater  activity  and  in- 
creased metabolism  in  the  individual  cells.  In  con- 
nection with  the  basal  connective  tissue  of  the  body  it 
is  difficult  to  grasp  the  idea  of  active  work;  to  attempt 
to  formulate  such  an  idea  may  perhaps  justly  lay  me 
open  to  the  charge  of  dealing  in  transcendental  pa- 
thology, and  yet,  as  I  shall  proceed  to  show,  a  consid- 


33 


eration  of  several  forms  of  ribrous-tissiie  hyperplasia 
in  connection  witii  the  dilTerent  or<jjans  and  diverse  in 
character,  forms  in  which  it  is  ditticult  tt)  decide  any 
clear  inHammator  orij^in,  leads  to  the  conclusion  that 
there  is  a  certain  bond  of  union  between  them,  that  in 
them  the  exi:itence  of  an  increased  strain  upon  the  tis- 
sue is  to  be  reco;j;nized,  and  that  if  we  could  group 
them  together  as  being  of  the  nature  of  "  functional" 
hyperplasias  or  hyperplasias  of  increased  function,  we 
should  advance  materially  in  our  grasp  and  compre- 
hension of  the  same. 

I  had  at  one  time  thought  that  increased  nutrition 
would  be  sufficient  to  explain  these  cases,  and  indeed 
1  have  l:)een  inclined  to  press  this  point  until  quite  re- 
cently. It  is  certainly  true  (as  is  best  shown  by  the  cases 
of  dystrophic  sclerosis  already  mentioned)  that  a  nu- 
trition insufficient  for  the  nobler  elements  of  an  organ 
suffices  often  for  the  active  growth  of  connective  tissue. 
This  fact  that  a  nutrition  ample  and  suitable  for  one 
tissue  does  not  suffice  for  another  has  long  attracted 
attention,  while  the  converse,  or  rather  the  corollary, 
was  proved  more  than  a  century  ago  by  John  Hunter 
in  his  classical  experiment  of  grafting  the  scantily- 
nourished  cock's  spur  upon  the  cock's  comb,  and  in 
this  richly  vascular  and  well-nourished  area  obtaining 
a  remarkable,  if  temporary,  hypertrophy  of  the  grafted 
organ.  Under  certain  conditions,  then,  active  increase 
of  nutrition  of  a  part  may  lead  to  hyperplasia  of  its 
cells.  Where  the  specific  cells  of  a  tissue  undergo 
atroph)  't  may  well  be  that  there  results  a  definite  in- 
crease in  the  amount  of  nutritive  fluid  at  the  disposal 
of  the  baser  interstitial  cells,  and  that  this  has  to  be 
taken  into  consideration  as  w^ell  as  any  more  direct 
stimulus  to  proliferation  afforded  by  the  products  of 
tissue  degeneration. 

If  this  be  so  we  are  met  with  the  likelihood  that  in 
conditions  tending  to  altered  nutrition  of  a  part — lead- 
ing to  the  tissues  becoming  bathed  with  lymph,  either 


34 


in  excess  of  the  needs  of  the  specific  and  nobler  cells 
of  that  tissue  or  of  a  quality  not  suited  for  the  uses  of 
those  cells— there  may  be  induced  an  overgrowth  of 
connective  tissue,  a  fibrosis,  to  be  ascribed  primarily 
to  nutritional  disturbances;  or,  in  other  words,  it  be- 
comes likely  that  there  may  be  nutritional  fibroses  as 
distinguished  from  inflammatory.  Plausible  as  this 
seems,  a  fuller  study  of  those  cases  which  at  first 
appear  to  be  examples  of  simple  nutritional  fibrous 
overgrowth  leads  to  the  conviction  that  there  is  some 
further  factor  also  at  work.  Or  otherwise,  increased 
nutrition,  even  if  long-continued,  does  not  inevitably 
lead  to  increased  connective-tissue  overgrowth,  and 
therefore  when  we  find  this  factor  most  in  evidence  in 
the  production  of  any  form  of  fibrosis  we  are  bound  to 
assume  that  there  must  be  some  additional  directive 
factor.  What  I  mean  will  best  be  shown  by  a  study 
of  the  cases  I  am  about  to  brins:  before  vou. 

Take  in  the  first  place  chronic  obstruction  to  the 
flow  of  lymph.  Where  such  obtains — whether  by  pres- 
sure of  tumors  upon  the  main  lymph  channels  of  a 
part,  by  blocking  of  the  same,  or  by  diseased  states  of 
the  lymph  glands — it  is  a  matter  of  frequent  observa- 
tion that  in  the  absence  of  satisfactory  collateral  tracts 
the  part  becomes  swollen  and  gradually  the  fluid  swell- 
ing gives  place  to  a  generalized,  if  not  very  extreme, 
connective-tissue  overgrowth.  In  such  cases  the  cir- 
culation of  the  blood  through  the  afi^ected  area  is  main- 
tained, there  are  no  positive  signs  of  inflammation  evi- 
dent either  macroscopically  or  microscopically.  We 
cannot  recognize  in  the  condition  an  attempt  at  repair. 
The  primary  injury  has  been  at  a  distance  from  the 
region  of  fibrosis.  Nevertheless,  it  may  be  argued  that 
the  stagnating  lymph  acts  in  these  cases  as  an  irritant 
to  the  connective-tissue  cells  and  that  the  condition 
must  be  regarded  as  a  productive  inflammatory  fibro- 
sis. 

While  this  view  deserves  full  consideration,  its  ac- 


35 


I 
■if 

I 


ceptance  must  lead  us  almost  inevitably  to  a  point  at 
which  we  become  bound  to  regard  as  of  inflammatory 
origin  every  condition  of  fibroid  overgrowth,  whatever 
be  the  stimulus.  Some  limit,  I  think,  must  be  given 
to  our  conception  of  what  is  included  in  the  process. 
It  will  be  seen  that  thus  far  every  example  given  by 
me  until  the  present  case  has  been  strictly  within  the 
limits  of  the  definition  laid  down,  namely,  it  has  been 
reparative  in  its  tendency  and  has  been  due  to  evident 
injury  to  the  part  which  becomes  the  seat  of  the  fibroid 
change.  We  must,  I  take  it,  decline  to  consider  a  le- 
sion as  an  infiammatory  fibrosis  in  the  development 
of  which  these  two  conditions  cannot  be  clearlv  recoc:- 
nized. 

Failing  inflammatory  origin,  can  we  regard  the  ex- 
ample given  above  as  being  brought  about  by  perverted 
nutrition  pure  and  simple?  1  am  inclined  to  think 
that  we  cannot.  We  should  expect  perverted  nutrition 
to  tell  first  upon  other  and  higher  tissues,  but  in  mai.y 
of  these  cases  we  find  singularly  little  evidence  of  pri- 
mary degeneration  of  nobler  tissues  (the  muscles  and 
skin  of  an  affected  extremity,  for  example).  Where 
the  circulation  of  healthy  blood  persists  through  such 
a  region  there  must  occur  constant  interchange  between 
blood  and  lymph,  and  the  blood  must  carry  away  the 
products  of  tissue  change  to  a  considerable  extent.  In 
deed  we  know  that  it  is  capable  of  vicariously  remo^'- 
ing  much  of  the  lymphatic  fluid.  With  our  present 
knowledge,  all  that  it  is  absolutely  safe  to  say  is  that 
we  are  here  dealing  with  a  quantitative  disturbance  in 
the  lymph  of  the  region,  coupled  with  a  mechanical 
disturbance,  namely,  increased  extravascular  and  in- 
terstitial pressure;  or,  to  put  it  otherwise,  the  cells  of 
the  connective  tissue  are  subjected  to  an  altered  ten- 
sion.   The  qualitative  disturbance  is  of  doubtful  extent. 

With  these  cases  of  obstructed  lymph  flow  in  a  part 
certain  examples  of  elephantiasis  Arabum  would  ap- 
pear to  be  classed — provisionally.     So  little  has  been 


36 


accomplished  in  establishing  the  real  nature  of  this 
disease,  or  more  truly  of  this  group  of  diseases,  that 
the  most  I  dare  venture  to  say  is  that  disturbed  out- 
flow of  lymph  from  the  affected  region  seems  to  be  in 
operation  in  some  cases  (elephantiasis  lymphangiec- 
tatica),  while  others  present  indications  of  venous  dis- 
turbance (elephantiasis  telangiectodes) ;  others  again 
(the  neuromatous  and  lipomatous  forms)  can  only 
safely  be  described  as  hypertrophic  conditions  ap- 
proaching peculiarly  close  to  generalized  neoplastic 
formation. 

Without  discussing  further  the  intimate  nature  of 
the  fibrous  hyperplasia  in  these  cases  at  the  present 
time,  let  me  pass  on  to  consider  another  class  of  cases. 
Increased  bathing  of  the  tissue  with  lymph  and  in- 
creased lymph  tension  may  also  result  from  active  and 
from  passive  hyperaimia.  From  either  of  these  causes 
there  may  be  passage  outward  of  lymph  from  the 
blood-vessels  in  amount  exceeding  the  efferent  capac- 
ity of  the  lymphatics.  Here  again  mere  increased 
amount  of  lymph  does  not  seem  to  lead  necessarily  to 
fibrosis.  Some  other  factor  or  factors  must  be  in- 
voked. Thus  in  the  liver,  while  extreme  congestion 
leads  especially  to  dilatation  of  the  vessels  with  pres- 
sure atrophy  of  the  specific  cells,  and  though  presuma- 
bly there  is  here  increased  exudation,  we  get  little  evi- 
dence of  fibrosis;  long-continued  moderate  congestion 
induces,  on  the  other  hand,  a  very  evident  fibrosis, 
most  marked,  it  is  true,  in  the  walls  of  and  immedi- 
ately around  the  intralobular  branches  of  the  hepatic 
vein,  but  seen  also  in  the  interstitial  substance  of  the 
neighborhood.  The  peculiar  arrangement  of  the  new 
fibrous  tissue  shows  that  it  cannot  be  regarded  simply 
as  an  example  of  replacement  fibrosis.  The  history 
in  these  cases  points  to  the  long-continued  action  of 
two  factors — increased  effusion  of  a  not  greatly  altered 
lymph  and  long-continued  (and  probably  varying)  pres- 
sure affecting  especially  the  central  parts  of  the  lobule. 


)f  this 
s,  that 
id  out- 
)  be  in 
ingiec- 
Lis  dis- 
again 
only 
ns  ap- 
plastic 

til  re  of 
Dresent 

cases, 
nd  in- 
ve  and 

causes 
t)m   the 

capac- 
creased 
arily  to 

be  in- 
gestion 
;h  pres- 
esuma- 
tle  evi- 
gestion 
ibrosis, 
iiimedi- 
hepatic 
;  of  the 
he  new 
simply 
history 
:tion  of 
altered 
g)  pres- 
lobule. 


The  relative  rarity  and  the  slight  extent  of  the 
fibrous  hyperplasia  accompanying  well-marked  passive 
congestion  is  in  itself  an  indication  that  the  quality 
of  the  effused  lymph  plays  a  part  in  the  development 
of  the  hyperplasia.  Neither  increased  amount  of 
lymph  of  poor  quality  in  a  part  nor  increased  intersti- 
tial tension  alone,  it  would  seem,  is  capable  of  induc- 
ing overgrowth. 

From  this  brief  and  hasty  consideration  of  fibroid 
changes  associated  with  the  lymphatic  and  venous  sys- 
tems which  are  not  to  be  regarded  as  of  inflammatory 
origin,  I  will  now  pass  on  to  discuss  in  somewhat 
greater  detail  what  appear  to  me  to  be  allied  condi- 
tions affecting  the  heart  and  arterial  system. 

In  ordinary  practice  apart  from  malformations,  neo- 
plasms, and  the  direct  effects  of  trauma,  the  patholog- 
ical changes  of  the  heart  valves  are  divided  into  the 
two  broad  classes  of  acute  and  chronic  endocarditis, 
and  although  the  non-committal  name  of  arterio-scle- 
rosis  is  in  frequent  use  and  although  its  employment 
appears  to  indicate  a  doubt  as  to  the  exact  etiology  of 
the  condition,  it  must,  I  think,  be  admitted  that  such 
arterio-sclerotic  changes  are  regarded  as  inflammatory 
in  character,  while  sporadically  the  attempt  is  made 
to  explain  them  by  suggesting  or  presupposing  the  ex- 
istence of  some  irritant  substance  in  the  blood  which 
by  direct  action  upon  the  vessel  walls  leads  to  injury 
and  to  reaction  in  the  shape  of  connective-tissue  over- 
growth. I  see,  for  example,  that  in  a  recent  number 
of  the  British  Medical  Journal  \\\^  apostle  of  uric  acid, 
Dr.  Haig,  suggests  that  a  cause  for  sclerosis  of  the 
heart  valves  is  to  be  found  in  the  irritant  action  of 
his  beloved  uric-acid  crvstals.' 

The  existence  of  inflammation  as  a  cause  of  sclero- 
sis is  more  frequently  to  be  determined  in  connection 

'  Alexander  Haig  :  "  Arthritis  and  Endocarditis  Due  to  Drugs 
which  Diminish  the  Solvent  Power  of  the  lilood  for  Uric  Acid," 
Britisli  Medical  Joiinial,  December  28,  1S95. 


38 


with  the  heart  valves  than  with  the  arterial  intima. 
Thus,  it  is  well  recognized  that  acute  valvular  disease 
may  be  followed  by  chronic  thickening  of  one  or  more 
segments,  that  similar  thickening  may  follow  rupture 
of  a  segment,  and  that  a  valvule  which  has  from  any 
cause  become  injured,  whether  from  simple  roughen- 
ing of  its  surface  or  more  usually  from  the  develop- 
ment upon  it  of  vegetations,  may  by  friction  induce 
inflammatory  disturbances  in  the  parts  with  which  it 
comes  into  contact. 

In  general  these  forms  present  an  irregular  or  vari- 
cose type  of  fibrosis,  but  it  is  often  difficult,  if  not  im- 
possible, to  distinguish  from  them  sundry  cases  of 
chronic  generalized  thickening  in  which  through  de- 
generation localized  disturbances  have  occurred  in  the 
thickened  valves  with,  it  may  be,  ulceration,  deposit 
of  fibrin,  and  subsequent  organization.  There  are, 
that  is  to  say,  doubtful  cases  in  which  it  is  practically 
impossible  to  declare  whether  we  are  dealing  with 
processes  following  upon  localized  valve  lesions  or 
with  the  sequelae  of  a  generalized  lesion. 

Apart  from  these  undoubtedly  the  most  common 
form  of  valve  lesion  met  with  in  the  post-mortem  the- 
atre is  a  generalized  thickening.  Perhaps  generalized 
is  not  a  wholly  correct  designation,  for  in  the  slightest 
forms  it  manifests  itself  more  especially  along  the 
edges  of  the  mitral  segments,  and  in  the  aortic  valvules 
it  is  below  the  line  of  apposition,  and  again  at  the  in- 
sertion of  each  segment,  that  the  fibrosis  is  most 
marked.  So  common  is  the  condition  that  in  general 
we  disregard  it  and,  accepting  it  as  almost  physiologi- 
cal, make  no  note  thereof.  But  in  the  examination 
of  a  series  of  hearts  we  may  pass  almost  impercep- 
tibly from  one  case  to  another  until  we  reach  condi- 
tions of  extreme  mitral  stenosis,  with  such  extensive 
generalized  thickening  of  the  whole  valve  and  conse- 
quent shortening  of  the  new  connective  tissue  laid 
down  that  the  mitral  veil  becomes  converted   into  a 


39 


:ima. 
sease 
more 
pture 
any 
;hen- 
elop- 
icluce 
ich  it 


circular  plate,  or  more  generally  into  a  short  blunt 
funnel  with  button-hole  passage.  And  we  come  across 
case  after  case  of  this  category  which  shows  no  sign 
of  localized  valvular  disturbance  either  old  or  recent. 
The  condition  affects  the  whole  of  the  valve  and  affects 
also  the  chorda:  tendinete,  which  are  thickened  and 
shortened. 

While  in  acute  endocarditis  and  in  the  nodose  or 
verrucose  sclerosis  following  upon  such  we  find  clear 
evidence  of  vascularization  of  the  valves,  and  sections 
show  fairly  frequent  vessels,  this  is  not  the  case  in 
the  generalized  thickening  here  referred  to.  The  es- 
sential characteristic  as  revealed  in  sections  is  the 
rarity  of  the  vessels;  the  fibrous  tissue  is  laid  down 
in  layers  parallel  to  the  surface,  and  the  most  recent, 
the  most  cellular  layers  are  those  nearest  to  the  endo- 
thelium— while  the  deepest  layers,  those  most  remote 
from  the  surface,  show  a  peculiar  tendency  to  degener- 
ative changes.  This  tendency  to  hyaline  swelling, 
fatty  degeneration,  and  other  evidences  of  necrobiosis 
—  in  short,  to  atheroma — is  in  itself  a  demonstration 
of  lack  of  due  vascularization  and  of  malnutrition. 
Indeed,  although  I  know  that  Luschka  and  others 
have  described  vessels  throughout  the  extent  of  the 
mitral  valve  segments,  my  own  injections  of  healthy 
hearts  of  several  species  have  led  me  to  the  more  gen- 
erally accepted  conclusion  that  the  outer  two-thirds  of 
the  mitral  are  almost,  of  the  aortic  valves  are  quite 
non-vascular,  and  to  the  further  conclusion  that 
healthy  valvules  gain  their  nutrition  in  the  main  from 
the  blood  circulating  within  the  heart.  It  is,  I  hold, 
by  passage  or  circulation  of  the  plasma  through  the 
stomata  of  the  lining  endothelial  cells  into  the  lymph 
spaces  between  the  layers  of  connective  tissue  forming 
the  supporting  frame  of  each  normal  valvule  that  the 
main  nutrition  of  the  non-vascular  areas  of  the  valves 
is  effected.  While  a  layer  of  the  vascular  myocardium 
is   contained  in  the  proximal  third  or  so  of  the  seg- 


40 


ments,  the  outer  two-thirds  is  scarce  anything  but  a 
fold  of  the  endocardium. 

That  the  endocardium  of  the  heart  in  general  gains 
its  nourishment  from  the  blood  within  the  chambers 
and  that  the  nourishing  plasma  may  even  extend  for 
some  little  distance  beyond,  is  very  prettily  shown  in 
some  cases  of  advanced  sclerosis  of  the  papillary  mus- 


FiG.  I. — Transverse  section  of  a  papillary  muscle  exhibiting  dystrophic 
sclerosis  to  show  xone  of  intact  muscle  fibres  immediately  beneath  the  en- 
docardium, a^  Layer  of  intact  muscle  fibres  beneath  endocardium  ;  />,  scle- 
rosed areas— replacement  of  atrophied  muscle  tissue  by  fibrous  tissue.  In  this 
are  venules  and  occasional  atrophied  .uiscle  fibres;  c\  arterioles  cut  trans- 
versely, exhibitinii'  thickened  and  sclerosed  coats,  and  surrounded  by  intact 
muscle  fibres;  </,  periarterial  sclerosis. 

cles,  which  present  complete  fibroid  metamorphosis  of 
the  central  area  of  the  pillars  with  a  zone  of  healthy 
fibres  all  around  the  periphery  immediately  beneath 
the  endocardium.  These  healthy  fibres  present  no  ac- 
companying arteries;  all  the  arterioles  coursing  up 
the  papillary  muscle  may  exhibit  advanced  proliferat- 
ing endarteritis.  The  only  and  the  obvious  expla- 
nation why  these  peripheral  fibres  remain  is  that  they 


41 


have  gained  their  nourishment  through  tlie  endocar- 
dium. 

Wherever  we  find  well-marked  vascularization  of  the 
outer  two-thirds  of  the  mitral  valve,  for  example,  we 
may  feel  assured  that  there  has  been  inflammation 
present.  The  vascularization  is  strictly  comparable 
to  that  obtaining  in  the  cornea  and  other  non-vascular 
areas,  and  indicates  a  development  secondary  to  acute 
disturbance  of  the  organ.  In  the  generalized  thicken- 
ing to  which  I  have  referred  one  is  struck  by  the  pecu- 
liar* rarity  or  almost  complete  absence  of  vessels  and 
by  the  fact  that  the  hypertrophic  fibroid  tissue  is  laid 
down  after  the  plan  of  the  normal  connective  layers  of 
the  region.  And  while  obviously  the  neAv  growth  is 
continuing  and  the  newest  tissue  is  situated  immedi- 
ately beneath  the  endothelium,  we  do  not  there  recog 
nize  any  characteristic  presence  of  small  round  cells. 
The  appearances  in  this  region  are  those  of  an  orderly 
hypertrophy. 

Two  hypotheses  may  be  adduced  to  explain  this 
state  of  affairs :  Either  that  the  sclerosis  is  of  inflam- 
matory origin,  the  residt  of  an  irritant  mild  in  charac- 
ter, causing  little  reaction  but  acting  continuously  over 
a  long  period,  or  that  it  is  non-inflammatory  and  com- 
parable to  the  fibroses  already  referred  to  in  connection 
with  the  lymphatic  system. 

It  is,  I  must  frankly  confess,  impossible  to  adduce 
sufficient  proof  to  entirely  refute  the  former  hypothesis 
— there  may  be  chronic  intoxications,  auto-intoxica- 
tions, or  otherwise,  due  to  substances  which  manifest  a 
special  tendency  to  act  upon  the  endocardium:  but 
such  substances  have  not  yet  been  isolated.  Increased 
pressure  upon  the  valves  may  directly  damage  them 
and  the  fibrosis  may  be  the  indication  of  a  reaction  to 
chronic  injury,  but  the  thickening  would  appear  to  be 
progressive  and  to  continue  until  a  condition  is  reached 
out  of  all  proportion  to  the  injury.  We  find,  therefore, 
no  absolute  and  sufficient  reason  for  regarding  the  con- 


42 


dition  as  of  inflammatory  origin.  Nevertheless,  the 
mere  fact  that  we  at  present  are  ignorant  of  any  imme- 
diate cause  for  the  production  of  this  lesion  is  not 
suflicient  ground  for  flatly  denying  the  existence  of 
such  cause,  and  even  the  fact  that  the  microscopic  ap- 
pearances are  not  those  of  ordinary  inflammation  is  not 
proof  positive  that  the  process  which  has  led  to  the 
lesion  has  not  been  essentially  of  an  inflammatory  na- 
ture. 

I  cannot,  that  is  to  say,  hold  it  proved  or  disproved 
that  generalized  sclerosis  of  the  cardiac  valves  is  in  all 
cases  of  inflammatory  nature.  And  the  matter  being 
thus  an  open  one,  it  may  be  well  to  hold  it  possible 
that  the  second  alternative  may  be  correct  and  to  seek 
for  evidence  in  support  of  it. 

Now,  it  is  interesting  to  note  that  just  those  conditions 
in  which  there  is  a  liability  for  the  production  of  gen- 
eralized thickening  of  the  heart  valves  are  clinically 
conditions  in  which  there  is  found  heightened  arterial 
tension,  conditions  which  also  bring  about  arterio-scle- 
rosis.  It  is  just  in  these  conditions  that  we  might  ex- 
pect to  have,  with  increased  pressure,  increased  nutri- 
tion of  the  endocardium  and  of  the  intima — increased 
passage  of  plasma  from  the  intracardiac  blood  through 
the  endothelium,  or  perhaps,  more  correctly,  between  the 
endothelial  cells.  And  I  cannot  but  consider  that  this 
increased  nutrition  coupled  with  increased  strain  may 
afford  a  satisfactory  explanation  for  this  condition  of 
so-called  chronic  endocarditis.  Such  a  proof  as  one 
would  desire  of  the  correctness  of  this  opinion  is  diffi- 
cult if  not  impossible  to  devise,  for  the  condition  is  the 
production  not  of  a  few  hours  but,  not  to  exaggerate,  of 
many  weeks.  Experiments  upon  the  subject  are  al- 
most if  not  quite  outside  the  range  of  experimental  pa- 
thology. Yet  certain  considerations  appear  to  support 
the  view.     Roy  and  I,'  for  example,  found  that  by  con- 

'  Roy  ami  Adami  :  "  On  Failure  of  the  Heart  from  Overstrain," 
British  Medical Jounial,  December  15,  1 888. 


43 


striding  the  first  part  of  the  aorta  in  the  clog  and  in 
the  rabbit  and  thereby  raising  the  blood  pressure  within 
the  heart,  we  were  able  in  the  course  of  a  few  minutes 
to  bring  about  the  production  of  numerous  small  pearly 
vesicles  along  the  edges  of  apposition  of  the  mitral  and 
aortic  valves,  and  we  could  onlv  account  for  this  devel- 
opment  by  assuming  that  with  the  increased  blood 
pressure  the  plasma  of  the  blood  had  been  driven  into 
the  substance  of  the  valve,  and  that  the  pearly  vesicles 
of  lymph  (or  plasma)  appeared  where  they  did  because 
at  these  regions  the  difference  between  the  pressure  on 
one  side  of  the  valve  segments  and  on  the  other  was  most 
in  evidence.  We  obtained,  so  we  held,  clear  proof  that 
with  increased  blood  pressure  increased  fluid  penetrates 
the  valve  substance.  It  is  important  to  note  that  simi- 
lar pearly  elevations  are  generally  regarded  as  the  first 
indication  of  valve  disease. 

But,  as  I  have  already  pointed  out,  it  is  unsafe  to  re- 
gard increased  nutrition  alone  as  a  cause  of  connective- 
tissue  hypertrophy,  and  if  we  cast  round  to  find  what 
other  factor  there  may  be  1  am  inclined  to  consider 
that  it  may  briefly  be  entitled  increased  strain  or  ten- 
sion acting  upon  the  individual  connective-tissue  cells. 

The  idea  may  at  first  appear  transcendental ;  we  are 
not  accustomed  to  think  of  the  connective-tissue  frame- 
work of  the  organism  as  being  strained  or,  to  carry  this 
view  to  its  logical  conclusion,  performing  work.  We 
only  regard  the  nobler  tissues  as  workers  — the  muscle 
fibres,  the  nerve  cells  and  the  specific  cells  of  the 
glands.  Nevertheless,  we  acknowledge  freely  that  in- 
creased work  thrown  upon  one  of  the  connective  tissues 
— namely,  bone  — does  lead  to  its  hypertrophy.  It  is 
a  matter  of  common  observation  that  not  only  are  the 
bones  of  those  accustomed  to  active  exercise  larger  and 
heavier  than  the  bones  of  the  sedentary,  but  also  that 
where  any  muscles  are  strongly  developed  there  bony 
ridges  and  bony  overgrowths  are  most  developed  at  their 
origins  and  insertions. 


44 


The  factors  leading  to  this  overgrowth  may  be 
suninied  up  under  the  comprehensive  title  of  increased 
work.  And  in  connection  w  ith  connective  tissue  where 
there  is  any  force  in  action  tending  to  draw  apart  and 
pull  upon  the  constituents  of  the  tissue — whether  the 
force  acts  from  without  or  (as  in  cases  of  increased 
effusion  of  lymph)  from  within  the  tissue — where,  in 
short,  there  is  a  strain  upon  the  components  of  the  tis- 
sue— there,  if  we  regard  the  work  of  the  connective  tis- 
sues, as  is  most  plausible,  as  being  to  bind  together  and 
support  other  tissues,  undoubtedly  that  work  is  in- 
creased and,  granting  that  at  the  same  time  the  nutrition 
remains  good,  we  have  a  condition  favorable  to  in- 
creased growth.  A /(>rt/(?r/ wti  img}\t  expect  such  hy- 
pertrophy where  simultaneously  the  amount  of  nutrition 
is  increased. 

I  suggest  this  very  tentatively,  for  I  have  a  horror  of 
far-fetched  pathology  and  an  accompanying  belief  that 
the  fuller  our  knowledge  of  a  subject  the  simpler  and 
more  straightforward  do  we  find  the  laws  governing  the 
associated  phenomena,  and  it  is  only  because  the  idea 
is  straightforward  and  is  in  harmony  with  our  knowl- 
edge of  occurrences  in  connection  with  other  tissues 
that  I  venture  to  formulate  it.  My  aim  in  these  lec- 
tures is  throughout  not  to  dictate  but  to  suggest  and 
call  attention  to  the  many  diverse  conditions  which  may 
bear  a  part  in  the  production  of  increased  fibrous  tis- 
sue. At  most  I  will  here  urge  that  it  is  possible  that 
increased  functional  activity  of  the  connective  tissues 
results  under  favojable  conditions  in  increased  growth 
of  the  same. 

Passing  now  to  the  arteries,  we  find  that  just  as  the 
muscular  walls  and  pericardium  of  the  heart  are  nour- 
ished by  the  coronary  vessels,  so  the  media  and  ad- 
ventitia  of  the  arteries  are  nourished  by  the  vasa 
vasorum,  whereas  in  health  the  intima  appears  to  be 
non-vascular.  Indeed,  where  it  is  well  developed,  the 
internal  elastic  lamina  appears  to  constitute  a  boun- 


45 


clary  line  between  the  vascular  and  non-vascular  areas 
of  the  arteries.  We  are  forced,  I  hold,  to  re<;ard  the 
intinia  as  nourished  from  the  blood  circulating^  within 
the  arteries. 

The  diseases  to  which  the  arterial  walls  are  subject 
are  closely  comparable  with  those  of  the  heart. 
There  can,  for  example,  be  undoubted  inflammation; 
we  may  even  have  collections  of  pus  cells  separating 
the  intima  from  the  media,  although  this  is  very 
rare  and  is  always  secondary  to  a  purulent  mesarte- 
ritis,  the  pus  cells  wandering  into  the  intima  from  the 
vessels  of  the  media.  Facu  in  cases  of  septic  embo- 
lism or  thrombosis,  necrosis  is  the  lirst  noticeable 
change  in  the  intima,  and  the  invasion  of  leucocytes 
appears  to  be  associated  with  the  later  inHammation 
of  the  media  and  adventitia.  Rather  more  frequent 
is  an  acute  productive  inHammation,  seen  especially  in 
the  first  portion  of  the  aorta.  'I'his  appears  to  be  sec- 
ondary to  simi;  ir  verrucose,  subacute,  and  ulcerous  in- 
flammation of  the  aortic  valvules.  It  is  characterized 
by  the  development  of  almost  papillomatous  or  warty 
processes  projecting  into  the  lumen  of  the  aorta,  and 
these  are  richly  cellular  and  also  vascularized  from  the 
vasa  vasorum.  They  are  often  covered  by  a  layer  of 
coagulum. 

But  these  ob\'iouslv  inHammatorv  conditions  are 
relatively  rare.  The  most  common  form  of  arterial 
disease  in  the  larger  arteries  is  that  termed  by  Vir- 
chow  endarteritis  chronica  nodosa  sive  deformans,  the 
arterio-sclerosis  of  Lobstein,  or  atheroma.  I  need  not 
here  enter  into  statistics  concerning  its  frequency,  or 
take  up  your  time  by  details  concerning  the  forms  that 
it  may  assume.  I  will  accept  Dr.  Councilman's  classi- 
fication,' simply  modifying  his  terminology  to  indicate 
my  doubts  as  to  the   endarteritic  or  inflammatory  na- 

^  Councilman:  "  On  the  Relations  between  Arterial  Disease  and 
Tissue  Changes. 


Trans.  Association  American  I'hysicians,  vi., 


1S91,  p.  179. 


4''' 


ture  of  tlic  coiulilions.  With  him,  therefore,  I  would 
clistin<;uish  i^a)  a  uocluhir  arterio-sclerosis,  {/>)  senile 
arterio-sclerosis,  and  (c)  diffuse  arlerio-sclerosis;  and 
would  with  him  acknowledge  that  these  three  forms 
merj^e  one  into  the  other,  l-'or  our  purpose,  as  throw- 
in*;  lijj;ht  upon  the  nature  of  the  conditif)n,  the  nodu- 
lar form,  the  true  endarteritis  nodosa  of  Virchow,  is 
that  to  which  I  would  more  especially  call  your  at- 
tention. 

'J'he  process  ]ie<:jins  l\v  the  development  of  semi- 
transparent,  almost  gelatinous,  plaques  here  and  there 
upon  the  walls  of  the  aorta  and  larger  vessels,  most 
often  in  the  neighborhood  of  and  around  the  orifice 
of  some  side  branch.  Where  the  process  is  older  the 
placjues  are  found  firm,  dense,  and  of  almost  cartilag- 
inous hardness,  and  with  this  stage  the  deeper  regions 
of  the  pla(.(ues  exhibit  manifest  degenerative  changes, 
passing  on  to  the  deposit  of  calcareous  salts  in  the 
necrol)iotic  substance. 

If  we  examine  these  plaques  we  are  struck  by  the 
following  peculiarities:  (i)  The  endothelium  over  the 
plaque  is  continuous  and  apparently  unaffected ;  (2) 
the  new  tissue  is  laid  down  regularly  in  layers  paral- 
lel to  the  endothelium;  (3)  the  connective  tissue  of 
the  intima  in  the  immediate  neighborhood  of  the 
plaque  passes  imperceptibly  into  the  hypertrophied 
connective  tissue  forming  the  plaque;  there  is  no 
boundary  line  to  be  made  out;  (4)  the  oldest  layers 
of  the  plaque  are  evidently  those  nearest  to  the  elastic 
lamina,  the  most  recent  are  beneath  the  endothelium 
and  farthest  away  from  the  vasa  vasorum  of  the  media; 
and  (5)  the  plaque  is  devoid  of  vessels  save  and  except 
in  those  cases  in  which  there  is  an  evident  attempt  at 
the  removal  of  the  necrosed  atheromatous  material,  and 
vessels  penetrate  into  the  atheromatous  mass  from  the 
media  in  a  manner  comparable  with  their  passage  into 
a  thrombus.  Such  passage,  it  will  be  recognized,  is 
of  purely  secondary  nature — the  fibrous  tissue  has  de- 


47 

veloped  and  undergone  degeneration  before  it  takes 
place. 

The  picture  presented  is  not  one  usually  associated 
with  intlamination.  The  picture  is  ratiier  what  we 
sh(Hild  exj^ect  to  find  in  an  orderly  connective-tissue 
hypertrophy,  while  the  degeneration  appearing  in  the 
deeper  layers  is  what  might  i)e  expecteil  to  occur  in  a 
non-vascular  area  in  which  layer  after  layer  of  con- 


Fir,.  2. — Section  of  the  Aorta  from  a  Case  of  N'odosc  Artcrio-scltrosis.  i, 
Thick  Ia\'er  of  iiypfrplastic  coniuTtivc  tisMic  iyinj,^  immccliatcly  bt-iicath  the 
endothfcliiim;  2,  hyaline  and  fatty  dcxciR-ration  of  tlic  lower  layers  of  tlie 
intinia;  3,  internal  layers  of  the  media,  staining  poorly  and  havin.i,'  a  liyahnd 
appearance;  4,  outer  layers  of  the  media— cellular  infiltration  around  the 
vasa  vasorum.i 

nective  tissue  cut  off  these  deeper  parts  from  their  or- 
dinary source  of  nutrition.  Indeed,  the  sharp  defini- 
tion of  the  necrosed  and  calcareous  tissue  at  the  in- 
ternal  elastic   lamina   is   often  very  remarkable  and 

'  For  this  specimen  and  that  from  which  Fig.  3  has  been  made 
I  am  indebted  to  Dr.  G.  H.  Mathewson,  who  is  studying  the 
cases  of  arterio-scierosis  occurring  at  the  Royal  Victoria  Hospi- 
tal, Montreal. 


48 


would  appear  not  only  to  afford  a  proof  of  the  correct- 
ness of  the  view  that  the  intima  is  nourished  from  the 
interior  of  the  artery,  but  also  would  suggest  that  the 
internal  elastic  lamina  performs  a  very  definite  func- 
tion in  separating  two  vascular  areas. 

This,  however,  is  not  the  whole  picture.  Con- 
stantly accompanying  and  indeed  preceding  the 
changes  in  the  intima,  there  is  to  be  recognized  an 
injury  or  degeneration  of  the  outer  coats,  whether 
of  specific,  inflammatory  causation  (as  in  cases  re- 
corded by  Thoma  and  Peabody),  or  whether  due  to 
more  obscure  alterations  in  nutrition  associated  with 
disturbances  of  the  vasa  vasorum.  In  many  cases 
these  small  vessels  are  congested  and  present  either  an 
infiltration  of  small  round  cells  in  their  immediate 
neighborhood  or  the  development  of  surrounding 
fibrous  tissue.  The  muscle  fibres  of  the  media  fre- 
quently exhibit  hyaline  and  other  degenerative 
changes,  and  there  may  be  some  replacement  fibrosis, 
or  again  evidences  of  more  extensive  failure  of  nutri- 
tion and  of  necrobiosis  in  the  shape  of  small  areas  of 
calcareous  deposit.  That  is  to  say,  the  media  is  very 
definitely  affected  and,  as  Thoma's  experiments  have 
fully  proved,  each  plaque  of  overgrowth  of  the  intima 
corresponds  to  a  localized  giving  way  of  the  arterial 
wall,  to  a  localized  slight  bulging  of  the  same;  for 
by  injecting  affected  arteries  with  paraffin  under  a 
pressure  of  one  hundred  and  sixty  millimetres  of  mer- 
cury, Thoma  obtained  a  smooth  cylindrical  mould 
showing  no  signs  of  depressions  corresponding  to  any 
projecting  plaques;  the  hypertrophied  intima  fills  and 
obliterates  the  slight  bulgings  or  pouches  of  the  outer 
coats.  However  produced,  there  can  be  no  question 
that  we  have  here  to  deal  with  a  compensatory  hyper- 
trophy of  the  intima. 

In  the  diffuse  form  also  Thoma  has  demonstrated 
that  the  growth  of  connective  tissue  in  the  intima  has 
a  similar  compensatory  nature. 


49 


Is  this  process  to  be  denominated  an  inflammation? 

Thoma  and  his  pupils  have  shown  that  a  thicken- 
ing of  the  intima  which  they  regard  as  strictly  analo- 
gous is  to  be  met  with  in  the  arteries  of  amputated 
limbs,  in  the  portion  of  the  aorta  between  the  ductus 
Botalli  and  the  offset  of  the  umbilical  arteries  imme- 
diately following  upon  birth,  in  the  uterine  arteries 
after  menstruation  has  set  in,  and  still  more  clearly 
after  childbirth;  so  to  a  less  extent  in  the  splenic  ar- 
teries. All  these  latter  cases  must  surely  be  classed 
among  physiological  rather  than  pathological  reac- 
tions. Surely  it  is  impossible  to  class  a  normal  con- 
stant change,  such  as  the  overgrowth  of  the  aortic 
intima  following  upon  birth,  as  an  inflammation.  Nev- 
ertheless Thoma  refers — or  referred — to  all  these  as 
conditions  of  compensatory  endarteritis.  But  if  he  is 
right — and  I  do  not  see  that  he  is  not — in  grouping 
all  these  cases,  physiological  and  pathological,  into 
one  common  class  and  ascribing  to  all  a  common 
causation,  then  not  one  ought  strictly  to  be  regarded 
as  of  inflammatory  origin. 

Thoma  would  explain  his  compensatory  endarteritis 
according  to  the  following  law,  namely,  that  the  con- 
dition is  to  be  ascribed  to  a  slowing  of  the  blood  cur- 
rent. If  this  slowing  be  not  arrested  by  a  contraction 
of  the  media  and  consequent  narrowing  of  the  artery, 
leading  to  more  rapid  flow,  then  there  occurs  a  new 
growth  in  the  intima  which  leads  to  the  same  end — 
causing  the  lumen  to  become  narrowed  and  the  cur- 
rent to  be  restored  to  its  normal  rate. 

He  thus  holds,  and  in  this  we  must  agree  with  him, 
that  the  primary  lesion  in  arterio-sclerosis  is  a  defect, 
a  giving  way,  of  the  media,  due  to  loss  of  elasticity 
however  produced — and  the  only  factor  that  he  judges 
capable  of  explaining  both  the  physiological  and  the 
pathological  cases  of  connective-tissue  overgrowth  in 
the  intima,  and  which  is  common  to  all  cases,  is  rela- 
tive slowing  of  the  blood  current.     It  is  difficult  to 


50 


follow  his  explanation  of  the  mechanism  whereby  such 
slowing  induces  the  hyperplasia  of  the  fibrous  tissue. 
Even  if  this  slowing  leads,  as  he  indicates,  to  func- 
tional disturbance  of  the  vasa  vasorum,  I  cannot  see 
how  these  vessels  influence  the  nutrition  of  the  intima. 
As  I  have  said,  I  cannot  find  evidence  that  in  healthy 
arteries  or  in  the  earlier  stages  of  arterio-sclerosis  any 
branches  of  these  vessels  pass  into  the  intima.  The 
process  within  the  "  bandelette  "  (as  French  histolo- 
gists  term  the  internal  elastic  lamina)  appears  to  be  at 
first  sharply  cut  off  from  that  occurring  outside  the 
same,  and  to  be  of  a  different  nature— the  new  growth 
does  not  appear  to  develop  from  the  neighborhood  of 


Fic;.  3.— Section  of  the  Aorta  from  a  Case  of  Nodose  Arlcrio-sclerosis,  to  show 
the  bulging  and  thiiininsj;  of  the  media,  prepared  by  Dr.  JMatliewson ; 
ma.Lcnified  8  diameters.  The  section  sliows  also  the  hyaline  de;tjeneration  of 
the  deeper  layers  of  the  overgrown  intima,  and  the  persistence  of  a  fine 
layer  of  less  altered  intima  tissue  immediately  beneath  the  media.  The 
media  in  this  case  showed  evidences  (jf  calcareous  degeneration  in  patches, 
with  some  hyaline  change. 

the  "  bandelette"  and  in  the  proximity  of  branches  of 
the  vasa  vasorum  entering  the  intima,  did  they  exist 
(save,  as  I  have  already  stated,  secondarily  to  degener- 
ative changes),  but  occurs  at  a  region  farthest  away 
from  such  branches.  At  most  a  thin  and  in  general 
hyaline  degenerated  layer  may  frequently  be  found 
lying  between  the  calcified  atheromatous  mass  in  the 
overgrown  intima  and  the  internal  elastic  lamina. 
This  would  indicate  that  a  small  amount  of  nutrition 
is  derived  from  the  media.  On  the  other  hand,  the 
examination  of  numerous  sections  would  indicate  that 
after  the  degeneration  of  the  lower  layers  of  the  intima 


51 

and  the  deposit  there  of  a  dense  calcareous  mass, 
growth  still  occurs  actively  and  new  layers  become 
formed  immediately  beneath  the  endothelium.  Were 
the  main  nutrition  from  the  vasa  vasorum  of  the  media 


'ic.  4. — Section  of  an  Arti'ry  of  Medi- 
um Size,  from  the  collection  at 
McGill  University.  ['I'his  had 
been  employed  as  a  test  specimen 
for  the  class  and  its  label  removed 
so  that  its  exact  oriifin  cannot  be 
stated.]       I,    Intact     endothelium; 

2,  layers    of     fibrous    hyperplasia  ; 

3,  hyaline  degeneration  of  the 
fibrous  tissue  ;  4,  layer  of  calcare- 
ous degeneration  lying  in  immediate: 
proximity  to  5,  the  internal  elas- 
tic lamina,  .somewhat  swollen  ;  6, 
media  presenting  no  distinct  evi- 
dences of  disease. 


Fk;.  5.— Section  of  Coronary  Artery 
from  a  Case  of  general  Arterio- 
.sclerosis,  to  show  the  persistence  of 
a  layer  of  but  slightly  altered  con- 
nective tissue  between  the  internal 
elastic  lamina  and  the  layer  of 
calcareous  degeneration.  In  this 
artery  there  had  evidently  been,  as 
indicated  at  4,  two  successive 
periods  of  sclerotic  thickening  of 
the  intima,  corresponding  to  a  giv- 
ing way  of  the  media  in  two  places. 


this  would  not  be  possible,  and  malnutrition  in  conse- 
quence of  disturbances  in  these  vessels  would  lead  to 
the  production  of  wedges  of  degeneration  extending 
toward  the  lumen,  rather  than  to  plaques  of  degenera- 


52 


tion  lying  deep  down  in  the  thickened  intima  close  to 
the  internal  elastic  lamina. 

Thus  I  cannot  but  conclude  that  disturbances  in  the 
vasa  vasorum  are  incapable  of  immediately  originat- 
ing the  changes  that  occur  in  the  intima.  There  may 
be  fibroid,  hyaline,  and  necrotic  changes  in  all  the 
coats  of  an  artery,  but  the  sequence  of  changes  in  the 
intima  does  not  maintain  a  strict  dependence  upon 
and  direct  association  with  the  sequence  in  the  media 
and  adventitia. 

Alterations  in  the  vasa  vasorum  failing  to  explain 
the  new  growth,  I  am  compelled  to  fall  back  upon  al- 
tered tension  as  a  factor  to  be  adduced  in  partial  ex- 
planation of  these  cases  of  increased  growth.  With 
Thoma  we  may  possibly  also  call  in  the  agency  of  the 
sensory  and  trophic  nerves  as  governing  the  growth, 
but  here  we  enter  further  upon  speculative  ground. 
They  may  play — they  probably  play — an  active  part, 
but  we  have  no  direct  evidence  that  they  do. 

The  most  that  we  can  safely  urge  is  that  with  rela- 
tive expansion  of  an  artery  or  portion  of  an  artery  there 
must  be  an  altered  tension  acting  upon  the  cells  of  the 
intima  of  the  affected  region — that  accepting  the  view 
that  the  intima  is  nourished  from  within  the  lumen, 
anything  which  will  lead  to  increased  passage  of  the 
blood  plasma  into  the  subendothelial  layers  of  the  in- 
tima may  at  the  same  time  lead  to  an  increased  strain 
upon  the  connective-tissue  cells  of  the  intima,  and  so 
to  increased  proliferation  of  the  same. 

If  this  be  so,  we  may  have  another  ground  than  the 
histological  appearance  for  regarding  the  condition  as 
non-inflammatory;  we  have  to  deal  with  a  stimulus 
rather  than  injury  to  the  cells  of  the  intima,  and  may 
see  in  the  fibrous  hyperplasia  a  response  to  a  physio- 
logical stimulus  rather  than  a  reaction  to  injury.  In 
any  case  with  our  present  knowledge,  limited  as  it  is,  I 
would  urge  that  the  non-committal  term  of  arterio- 
sclerosis is  preferable  to  that  of  chronic  endarteritis. 


53 


Than  this  latter  the  term  chronic  arteritis  is  more  ac- 
ceptable, for  in  connection  with  the  artery  as  a  whole 
as  distinguished  from  the  intima  there  is  in  the  giving 
way  and  thinning  of  the  media  evidence  of  injury,  and 
in  the  intima  as  well  as  in  the  media,  and  it  may  be 
in   the   adventitia  also,  evidence   of   repair — of   the 


■-W 


CL 


:£S* 


"^-•C 


..•*».. 


0. 


Fig.  6. — From  a  Section  of  the  left  Ventricle  of  a  Patient  dyinjj;  from  aortic 
stenosis  with  general  arterio-sclerosis,  to  show  mixed  dystrophic  (ci)  and 
periarterial  fibrosis  {//). 

artery  as  a  whole,  not  of  the  intima ;  an  arteritis,  not 
an  endarteritis. 

The  distinction  I  admit  is  fine  drawn,  yet  I  am  com- 
pelled to  acknowledge  that  it  exists.  I  cannot  ac- 
knowledge a  physiological  inflammation,  and  if,  as 
Thoma  points  out,  the  initial  process  is  identical  in 
physiological  overgrowth  of  the  intima  and  that  occur- 


54 


ring  in  arterio-sclerosis,  then  the  latter  process  must 
be  regarded  as  functional.  Were  some  irritant  discov- 
ered capable  of  directly  inducing  the  hyperplasia  of 
the  intima,  the  case  might  present  a  different  facies. 
That  such  i  ;  irritant  exists  is,  it  seems  to  me,  highly 
improbable.  The  peculiar  contrast  between  the  pul- 
monary and  the  systemic  arteries  in  their  liability  to 
arterio-sclerotic  changes  is  strongly  suggestive  of  the 
action  of  differences  in  the  circulation  as  explaining 
the  contrast  and  not  of  the  action  of  any  irritative 
component  of  the  blood. 

I  do  but  suggest  this,  and  suggest  it  most  tentative- 
ly. I  shall  feel  rewarded  if  the  suggestion  leads  to 
increased  study  into  the  phenomena  underlying  some 
of  the  commonest  and  most  important  forms  of  con- 
nective-tissue overgrowth.  We  are  so  woefully  igno- 
rant of  the  causation  of  such  common  conditions  as 
chronic  valve  disease  and  arterio-sclerosis  that  I  feel 
that,  even  if  the  views  here  enunciated  originate  strong 
and  successful  opposition,  the  stimulus  they  may  have 
given  to  further  investigation  will  be  an  ample 
reward. 

The  whole  matter,  as  it  appears  to  me,  resolves  it- 
self into  this :  "  Can  we  regard  fibrous  connective  tis- 
sue as  following  the  same  laws  as  the  higher  tissues 
and  so  as  undergoing  hypertrophy  in  consequence  of 
increased  work  or  increased  strain  brought  to  bear 
upon  it?"  If  we  can,  then  it  would  seem  that  we  can 
divide  off  an  important  series  of  fibroses  from  the 
huge  class  of  inflammatory  fibroses.  If  we  cannot, 
then  we  must  continue  to  regard  all  fibroses  save  the 
neoplastic  as  chronic  "  itides." 

Provisionally,  therefore,  I  would  divide  the  various 
forms  of  fibrosis  as  shown  in  the  diagram,  namely: 

A.  Of  inflammatory  origin  : 

1.  Replacement. 

2.  Productive. 


J  St 
)V- 

of 
es. 
ily 
il- 
to 
he 

ng 
ve 


re.- 
to 
ne 
>n- 

10- 

as 
id 

ng 
ve 

)le 

it- 

is- 
es 
of 
;ar 
an 
he 

Dt, 

he 
us 


55 


3.  Combined  productive  and  replacement. 

4.  Neoplastic. 

B.  Neoplastic,  of  undetermined  causation: 

I.  True  fibromata. 

C.  Of  functional  origin : 

1.  Lymphatic. 

2.  Venous. 

3.  Arterial. 

There  are  very  many  individual  cases  of  fibroid 
change  that  I  have  not  discussed  in  these  two  lectures. 
To  have  done  so  would  have  consumed  too  much  time 
and  would  have  carried  us  still  farther  into  conjectural 
regions.  But  the  cases  that  I  have  brought  before  you 
represent,  1  believe,  the  main  types  of  fibrosis;  and 
those  not  here  taken  into  consideration  will,  I  believe, 
fall  into  one  or  other  of  the  main  classes  here  indi- 
cated. 

In  conclusion  I  beg,  Mr.  President,  to  thank  you 
and  all  the  members  for  your  great  courtesy  in  endur- 
ing so  patiently  the  long  discourse  that  I  have  in- 
flicted upon  you,  and  once  again  to  thank  you  for  the 
honor  you  have  conferred  upon  me  in  inviting  me  to 
deliver  these  lectures. 


